Search results for: anticancer
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 310

Search results for: anticancer

100 The Metabolite Profiling of Fulvestrant-3 Boronic Acid under Biological Oxidation

Authors: Changde Zhang, Qiang Zhang, Shilong Zheng, Jiawang Liu, Shanchun Guo, Qiu Zhong, Guangdi Wang

Abstract:

Fulvestrant was approved by FDA to treat breast cancer as a selective estrogen receptor downregulator (SERD) with intramuscular injection administration. ZB716, a fulvestarnt-3 boronic acid, is an SERD with comparable anticancer effect to fulvestrant, but could produce good pharmacokinetic properties under oral administration with mice or rat models. To understand why ZB716 produced much better oral bioavailability, it was proposed that the boronic acid blocked the phase II direct biotransformation with the hydroxyl group on the 3 position of the aromatic ring on fulvestrant. In this study, ZB716 or fulvestrant was incubated with human liver microsome and oxidation cofactor NADPH in vitro. Their metabolites after oxidation were profiled with the Q-Exactive, a high-resolution mass spectrometer. The result showed that ZB716 blocked the forming of hydroxyl groups on its benzene ring except for the oxidation of C-B bond forming fulvestrant in its metabolites, and the concentration of fulvestrant with one more hydroxyl group found in the metabolites from incubation with fulvestrant was about 34 fold high as that formed from incubation with ZB716. Compared to fulvestrant, ZB716 is expected to be much difficult to be further bio-transformed into more hydrophilic compounds, to be difficult excreted out of blood system, and to have longer residence time in blood, which can lead to higher oral bioavailability. This study provided evidence to explain the high bioavailability of ZB716 after oral administration from the perspective of its difficulty of oxidation, a phase I biotransformation, on positions on its aromatic ring.

Keywords: biotransformation, fulvestrant, metabolite profiling, ZB716

Procedia PDF Downloads 259
99 Pattern of Adverse Drug Reactions with Platinum Compounds in Cancer Chemotherapy at a Tertiary Care Hospital in South India

Authors: Meena Kumari, Ajitha Sharma, Mohan Babu Amberkar, Hasitha Manohar, Joseph Thomas, K. L. Bairy

Abstract:

Aim: To evaluate the pattern of occurrence of adverse drug reactions (ADRs) with platinum compounds in cancer chemotherapy at a tertiary care hospital. Methods: It was a retrospective, descriptive case record study done on patients admitted to the medical oncology ward of Kasturba Hospital, Manipal from July to November 2012. Inclusion criteria comprised of patients of both sexes and all ages diagnosed with cancer and were on platinum compounds, who developed at least one adverse drug reaction during or after the treatment period. CDSCO proforma was used for reporting ADRs. Causality was assessed using Naranjo Algorithm. Results: A total of 65 patients was included in the study. Females comprised of 67.69% and rest males. Around 49.23% of the ADRs were seen in the age group of 41-60 years, followed by 20 % in 21-40 years, 18.46% in patients over 60 years and 12.31% in 1-20 years age group. The anticancer agents which caused adverse drug reactions in our study were carboplatin (41.54%), cisplatin (36.92%) and oxaliplatin (21.54%). Most common adverse drug reactions observed were oral candidiasis (21.53%), vomiting (16.92%), anaemia (12.3%), diarrhoea (12.3%) and febrile neutropenia (0.08%). The results of the causality assessment of most of the cases were probable. Conclusion: The adverse effect of chemotherapeutic agents is a matter of concern in the pharmacological management of cancer as it affects the quality of life of patients. This information would be useful in identifying and minimizing preventable adverse drug reactions while generally enhancing the knowledge of the prescribers to deal with these adverse drug reactions more efficiently.

Keywords: adverse drug reactions, platinum compounds, cancer, chemotherapy

Procedia PDF Downloads 429
98 Anticancer Effect of Isolated from the Methanolic Extract of Triticum Aestivum Straw in Mice

Authors: Savita Dixit

Abstract:

Rutin is the bioactive flavonoid isolated from the straw part of Triticum aestivum and possess various pharmacological applications. The aim of this study is to evaluate the chemopreventive potential of rutin in an experimental skin carcinogenesis mice model system. Skin tumor was induced by topical application of 7, 12-dimethyl benz(a) anthracene (DMBA) and promoted by croton oil in Swiss albino mice. To assess the chemopreventive potential of rutin, it was orally administered at a concentration of (200 mg/kg and 400 mg/kg body weight) continued three times weekly for 16th weeks. The development of skin carcinogenesis was assessed by histopathological analysis. Reductions in tumor size and cumulative number of papillomas were seen due to rutin treatment. Average latent period was significantly increased as compared to carcinogen-treated control. Rutin produced a significant decrease in the activity of serum enzyme serum glutamate oxalate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP) and bilirubin when compared with the control. They significantly increased the levels of enzyme involved in oxidative stress glutathione (GSH), superoxide dismutase (SOD) and catalase. The elevated level of lipid peroxidase in the control group was significantly inhibited by rutin administration. The results of the present study suggest the chemopreventive effect of rutin in DMBA and croton oil-induced skin carcinogenesis in swiss albino mice and one of the probable reasons would be its antioxidant potential.

Keywords: chemoprevention, papilloma, rutin, skin carcinogenesis

Procedia PDF Downloads 338
97 Survey of the Effect of the Probiotic Bacterium Lactobacillus plantarum and Streptococcus mutans on Casp3, AKT/PTEN, and MAPK Signaling Pathways at Co-Culture with KB Oral Cancer Cell Line and HUVEC Cells

Authors: Negar Zaheddoust, Negin Zaheddoust, Abbas Asoudeh-Fard

Abstract:

Probiotic bacteria have been employed as a novel and less side-effect strategy for anticancer therapy. Since the oral cavity is a host for probiotic and pathogen bacteria to colonize, more investigation is needed to evaluate the effectiveness of this novel adjunctive treatment for oral cancer. We considered Lactobacillus plantarum as a probiotic and Streptococcus mutans as a pathogen bacterium in our study. The aim of this study is to examine the effect of Lactobacillus plantarum and Streptococcus mutans on Casp3, AKT / PTEN, and MAPK signaling pathway, which is involved in apoptosis or survival of oral cancer KB cells. On the other hand, to study the effects of these bacteria on normal cells, we used HUVEC cells. The KB and HUVEC cell lines were co-cultured with Lactobacillus plantarum and Streptococcus mutans isolated from traditional Iranian dairy and dental plaque, respectively. The growth-inhibitory effects of these two bacteria on KB and HUVEC cells were determined by (3-(4, 5-dimethylthiazolyl-2)-2,5diphenyltetrazolium bromide) MTT assay. MTT results demonstrated that the proliferation of KB cells was affected in a time, dose, and strain-dependent manner. In the following, the examination of induced apoptosis or necrosis in co-cultured KB cells with the best IC50 concentration of the Lactobacillus plantarum and Streptococcus mutans will be analyzed by FACS flow cytometry, and the changes in gene expression of Casp3, AKT / PTEN, MAPK genes will be evaluated using real-time polymerase chain reaction.

Keywords: cancer therapy, induced apoptosis, oral cancer, probiotics

Procedia PDF Downloads 248
96 Induction of Cytotoxicity and Apoptosis in Ovarian Cancer Cell Line (CAOV-3) by an Isoquinoline Alkaloid Isolated from Enicosanthellum pulchrum (King) Heusden

Authors: Noraziah Nordin, Najihah Mohd Hashim, Nazia Abdul Majid, Mashitoh Abdul Rahman, Hamed Karimian, Hapipah Mohd Ali

Abstract:

Enicosanthellum pulchrum belongs to family Annonaceae is also known as family of 'mempisang' in Malaysia. Liriodenine was isolated by prep-HPLC method. This method was first technique used for the isolation of this compound. The structure of the liriodenine was elucidated by 1D and 2D spectroscopy techniques. Liriodenine was tested on ovarian cancer cells line (CAOV-3) for MTT, AO/PI and cytotoxicity 3 assays. The MTT assay was performed to determine the cytotoxicity effect of lirodenine on CAOV-3 cells. The morphological changes on CAOV-3 cells were observed by AO/PI assay for the early and late stage of apoptosis, as well as necrosis. Meanwhile, the measurement of cell loss, nuclear morphology, DNA content, cell membrane permeability, mitochondrial membrane potential changes and cytochrome c release from mitochondria were detected through cytotoxicity 3 assay. The IC50 results showed liriodenine inhibits the growth of CAOV-3 cells after 24 h of treatment at 10.25 ± 1.06 µg/mL. After 48 and 72 h of treatments, the IC50 values were decreased to 7.65 ± 0:07 and 6.35 ± 1.62 µg/mL, respectively. The morphology changes can be seen on CAOV-3 with a production of cell membrane blebbing, cromatin condensation and apoptotic bodies with increasing time of treatment from 24 to 72 h. Evaluation of cytotoxicity 3 on CAOV-3 cells after treated with liriodenine, resulting loss of mitochondrial membrane potential and release of cytochrome c from mitochondria. The results demonstrated the capability of liriodenine as a promising anticancer agent, particularly on human ovarian cancer.

Keywords: Enicosanthellum pulchrum, ovarian cancer, apoptosis, cytotoxicity

Procedia PDF Downloads 444
95 Assessment of Isatin as Surface Recognition Group: Design, Synthesis and Anticancer Evaluation of Hydroxamates as Novel Histone Deacetylase Inhibitors

Authors: Harish Rajak, Kamlesh Raghuwanshi

Abstract:

Histone deacetylase (HDAC) are promising target for cancer treatment. The panobinostat (Farydak; Novartis; approved by USFDA in 2015) and chidamide (Epidaza; Chipscreen Biosciences; approved by China FDA in 2014) are the novel HDAC inhibitors ratified for the treatment of patients with multiple myeloma and peripheral T cell lymphoma, respectively. On the other hand, two other HDAC inhibitors, Vorinostat (SAHA; approved by USFDA in 2006) and Romidepsin (FK228; approved by USFDA in 2009) are already in market for the treatment of cutaneous T-cell lymphoma. Several hydroxamic acid based HDAC inhibitors i.e., belinostat, givinostat, PCI24781 and JNJ26481585 are in clinical trials. HDAC inhibitors consist of three pharmacophoric features - an aromatic cap group, zinc binding group (ZBG) and a linker chain connecting cap group to ZBG. Herein, we report synthesis, characterization and biological evaluation of HDAC inhibitors possessing substituted isatin moiety as cap group which recognize the surface of active enzyme pocket and thiosemicarbazide moiety incorporated as linker group responsible for connecting cap group to ZBG (hydroxamic acid). Several analogues were found to inhibit HDAC and cellular proliferation of Hela cervical cancer cells with GI50 values in the micro molar range. Some of the compounds exhibited promising results in vitro antiproliferative studies. Attempts were also made to establish the structure activity relationship among synthesized HDAC inhibitors.

Keywords: HDAC inhibitors, hydroxamic acid derivatives, isatin derivatives, antiproliferative activity, docking

Procedia PDF Downloads 307
94 Effects of a Bioactive Subfraction of Strobilanthes Crispus on the Tumour Growth, Body Weight and Haematological Parameters in 4T1-Induced Breast Cancer Model

Authors: Yusha'u Shu'aibu Baraya, Kah Keng Wong, Nik Soriani Yaacob

Abstract:

Strobilanthes crispus (S. crispus), is a Malaysian herb locally known as ‘Pecah kaca’ or ‘Jin batu’ which have demonstrated potent anticancer effects in both in vitro and in vivo models. In particular, S. crispus subfraction (SCS) significantly reduced tumor growth in N-methyl-N-Nitrosourea-induced breast cancer rat model. However, there is paucity of information on the effects of SCS in breast cancer metastasis. Thus, in this study, the antimetastatic effects of SCS (100 mg/kg) was investigated following 30 days of treatment in 4T1-induced mammary tumor (n = 5) model. The response to treatment was assessed based on the outcome of the tumour growth, body weight and hematological parameters. The results demonstrated that tumor bearing mice treated with SCS (TM-S) had significant (p<0.05) reduction in the mean tumor number and tumor volume as well as tumor weight compared to the tumor bearing mice (TM), i.e. tumor untreated group. Also, there was no secondary tumor formation or tumor-associated lesions in the major organs of TM-S compared to the TM group. Similarly, comparable body weights were observed among the TM-S, normal (uninduced) mice treated with SCS and normal (untreated/control) mice (NM) groups compared to the TM group (p<0.05). Furthermore, SCS administration does not cause significant changes in the hematological parameters as compared to the NM group, which indicates no sign of anemia and toxicity related effects. In conclusion, SCS significantly inhibited the overall tumor growth and metastasis in 4T1-induced breast cancer mouse model suggesting its promising potentials as therapeutic agent for breast cancer treatment.

Keywords: 4T1-cells, breast cancer, metastasis, Strobilanthes crispus

Procedia PDF Downloads 151
93 Exploring Paper Mill Sludge and Sugarcane Bagasse as Carrier Matrix in Solid State Fermentation for Carotenoid Pigment Production by Planococcus sp. TRC1

Authors: Subhasree Majumdar, Sovan Dey, Sayari Mukherjee, Sourav Dutta, Dalia Dasgupta Mandal

Abstract:

Bacterial isolates from Planococcus genus are known for the production of yellowish orange pigment that belongs to the carotenoid family. These pigments are of immense pharmacological importance as antioxidant, anticancer, eye and liver protective agent, etc. The production of this pigment in a cost effective manner is a challenging task. The present study explored paper mill sludge (PMS), a solid lignocellulosic waste generated in large quantities from pulp and paper mill industry as a substrate for carotenoid pigment production by Planococcus sp. TRC1. PMS was compared in terms of efficacy with sugarcane bagasse, which is a highly explored substrate for valuable product generation via solid state fermentation. The results showed that both the biomasses yielded the highest carotenoid during 48 hours of incubation, 31.6 mg/gm and 42.1 mg/gm for PMS and bagasse respectively. Compositional alterations of both the biomasses showed reduction in lignin, hemicellulose and cellulose content by 41%, 15%, 1% for PMS and 38%, 25% and 6% for sugarcane bagasse after 72 hours of incubation. Structural changes in the biomasses were examined by FT-IR, FESEM, and XRD which further confirmed modification of solid biomasses by bacterial isolate. This study revealed the potential of PMS to act as cheap substrate for carotenoid pigment production by Planococcus sp. TRC1, as it showed a significant production in comparison to sugarcane bagasse which gave only 1.3 fold higher production than PMS. Delignification of PMS by TRC1 during pigment production is another important finding for the reuse of this waste from the paper industry.

Keywords: carotenoid, lignocellulosic, paper mill sludge, Planococcus sp. TRC1, solid state fermentation, sugarcane bagasse

Procedia PDF Downloads 235
92 Evaluation of Cytotoxic Effect of Mitoxantrone Conjugated Magnetite Nanoparticles and Graphene Oxide-Magnetite Nanocomposites on Mesenchymal Stem Cells

Authors: Abbas Jafarizad, Duygu Ekinci

Abstract:

In this work targeted drug delivery is proposed to decrease adverse effect of drugs with concomitant reduces in consumption and treatment outgoings. Nanoparticles (NPs) can be prepared from a variety of materials such as lipid, biodegradable polymer that prevent the drugs cytotoxicity in healthy cells, etc. One of the most important drugs used in chemotherapy is mitoxantrone (MTX) which prevents cell proliferation by inhibition of topoisomerase II and DNA repair; however, it is not selective and has some serious side effects. In this study, mentioned aim is achieved by using several nanocarriers like magnetite (Fe3O4) and their composites with magnetic graphene oxide (Fe3O4@GO). Also, cytotoxic potential of Fe3O4, Fe3O4-MTX, and Fe3O4@GO-MTX nanocomposite were evaluated on mesenchymal stem cells (MSCs). In this study, we reported the synthesis of monodisperse Fe3O4 NPs and Fe3O4@GO nanocomposite and their structures were investigated by using field emission scanning electron microscope (FESEM), Fourier transform infrared (FTIR) spectra, atomic force microscopy (AFM), Brauneur Emmet Teller (BET) isotherm and contact angle studies. Moreover, we used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to evaluate cytotoxic effects of MTX, Fe3O4 NPs, Fe3O4-MTX and Fe3O4@GO-MTX nanocomposite on MSCs. The in-vitro MTT results indicated that all concentrations of MTX and Fe3O4@GO-MTX nanocomposites showed cytotoxic effects while all concentrations of Fe3O4 NPs and Fe3O4-MTX NPs did not show any cytotoxic effect on stem cells. The results from this study indicated that using Fe3O4 NPs as anticancer drug delivery systems could be a trustworthy method for cancer treatment. But for reaching excellent and accurate results, further investigation is necessary.

Keywords: mitoxantrone, magnetite, magnetic graphene oxide, MTT assay, mesenchymal stem cells

Procedia PDF Downloads 272
91 Development of Nanoparticulate Based Chimeric Drug Delivery System Using Drug Bioconjugated Plant Virus Capsid on Biocompatible Nanoparticles

Authors: Indu Barwal, Shloka Thakur, Subhash C. Yadav

Abstract:

The plant virus capsid protein based nanoparticles are extensively studied for their application in biomedical research for development of nanomedicines and drug delivery systems. We have developed a chimeric drug delivery system by controlled in vitro assembly of separately bioconjugated fluorescent dye (as reporting molecule), folic acid (as receptor binding biomolecule for targeted delivery) and doxorubicin (as anticancer drug) using modified EDC NHS chemistry on heterologously overexpressed (E. coli) capsid proteins of cowpea chlorotic mottle virus (CCMV). This chimeric vehicle was further encapsidated on gold nanoparticles (20nm) coated with 5≠ thiolated DNA probe to neutralize the positive charge of capsid proteins. This facilitates the in vitro assembly of modified capsid subunits on the gold nanoparticles to develop chimeric GNPs encapsidated targeted drug delivery system. The bioconjugation of functionalities, number of functionality on capsid subunits as well as virus like nanoparticles, structural stability and in vitro assembly were confirmed by SDS PAGE, relative absorbance, MALDI TOF, ESI-MS, Circular dichroism, intrinsic tryptophan fluorescence, zeta particle size analyzer and TEM imaging. This vehicle was stable at pH 4.0 to 8.0 suitable for many organelles targeting. This in vitro assembled chimeric plant virus like particles could be suitable for ideal drug delivery vehicles for subcutaneous cancer treatment and could be further modified for other type of cancer treatment by conjugating other functionalities (targeting, drug) on capsids.

Keywords: chimeric drug delivery vehicles, bioconjugated plant, virus, capsid

Procedia PDF Downloads 493
90 Anatomical and Histological Characters of Cymbopogon nardus Roots and Its Mutagenic Properties

Authors: Pravaree Phuneerub, Chanida Palanuvej, Nijsiri Ruangrungsi

Abstract:

Cymbopogon nardus Rendel (Family Gramineae) is commonly known as citronella grass. The dried root of C. nardus is used for antipyretic, anti-inflammation, anti-analgesic and anticancer in traditional Thai medicine. Transverse sectional and pulverized C. nardus root were illustrated. The volatile oil was extracted from oil gland by hydrodistillation and analysed by GC/MS. Cymbopogon nardus root was exhaustively extracted by continuously maceration in ethanol and water respectively. The mutagenic and antimutagenic properties of the ethanol extract and fractionated water extract of C. nardus root were evaluated by Ames assay using the S. typhimurium strains TA98 and TA100 as the models. The result indicated that the anatomical character of root transverse section displayed epidermis, parenchyma, oil gland, phloem, xylem vessel, endodermis and pith. Histological characters of root powder showed parenchyma containing oleoresin, parenchyma in longitudinal view, reticulate vessel, annular vessel, starch granules and fragment of fiber. The root volatile oil was rich in sesquiterpenes dominated by elemol (22.87%) and alpha-eudesmol (16.09%). For mutagenic activity, the both extracts of C. nardus were no mutagenic toward S. typhimurium strains TA98 and TA100. Furthermore, the ethanol extract and fractionated water extract of C. nardus root demonstrated strong antimutagenic effect against of nitrite treated 1-aminopyrene to S. typhimurium strains TA98 and TA100. This present investigation suggested that the dried root extract of C. nardus can be further developed as promising antimutagenic agent.

Keywords: Cymbopogon nardus, volatile oil analysis, mutagenic, antimutagenic effect, Ames Salmonella assay

Procedia PDF Downloads 345
89 The Activity of Polish Propolis and Cannabidiol Oil Extracts on Glioblastoma Cell Lines

Authors: Sylwia K. Naliwajko, Renata Markiewicz-Zukowska, Justyna Moskwa, Krystyna Gromkowska-Kepka, Konrad Mielcarek, Patryk Nowakowski, Katarzyna Socha, Anna Puscion-Jakubik, Maria H. Borawska

Abstract:

Glioblastoma (grade IV WHO) is a rapidly progressive brain tumor with very high morbidity and mortality. The vast malignant gliomas are not curable despite the therapy (surgical, radiotherapy, chemotherapy) and patients seek alternative or complementary treatments. Patients often use cannabidiol (CBD) oil as an alternative therapy of glioblastoma. CBD is one of the cannabinoids, an active component of Cannabis sativa. THC (Δ9-tetrahydrocannabinol) can be addictive, and in many countries CBD oil without THC ( < 0,2%) is available. Propolis produced by bees from the resin collected from trees has antiglioma properties in vitro and can be used as a supplement in complementary therapy of gliomas. The aim of this study was to examine the influence of extract from CBD oil in combination with propolis extract on two glioblastoma cell lines. The MTT (Thiazolyl Blue Tetrazolium Bromide) test was used to determine the influence of CBD oil extract and polish propolis extract (PPE) on the viability of glioblastoma cell lines – U87MG and LN18. The cells were incubated (24, 48 and 72 h) with CBD oil extract and PPE. CBD extract was used in concentration 1, 1.5 and 3 µM and PPE in 30 µg/mL. The data were presented compared to the control. The statistical analysis was performed using Statistica v. 13.0 software. CBD oil extract in concentrations 1, 1.5 and 3 µM did not inhibit the viability of U87MG and LN18 cells (viability more than 90% cells compared to the control). There was no dose-response viability, and IC50 value was not recognized. PPE in the concentration of 30 µg/mL time-dependently inhibited the viability of U87MG and LN18 cell line (after 48 h the viability as a percent of the control was 59,7±6% and 57,8±7%, respectively). In a combination of CBD with PPE, the viability of the treated cells was similar to PPE used alone (58,2±7% and 56,5±9%, respectively). CBD oil extract did not show anti-glioma activity and in combination with PPE did not change the activity of PPE.

Keywords: anticancer, cannabidiol, cell line, glioblastoma

Procedia PDF Downloads 246
88 In Vitro Evaluation of the Antimitotic and Genotoxic Effect by the Allium cepa L. Test of the Aqueous Extract of Peganum harmala L. Leaves (Laghouat, Algeria)

Authors: Ouzid Yasmina, Aiche-Iratni Ghenima, Harchaoui Lina, Saadoun Noria, Houali Karim

Abstract:

Medicinal plants are an important source of bioactive molecules with biological activities such as anticancer, antioxidant, anti-inflammatory, antibacterial, antimitotic.... These molecules include alkaloids, polyphenols and terpenes. The latter can be extracted by different solvents, namely: water, ethanol, methanol, butanol, acetone... This is why it seemed interesting to us to evaluate in vitro the antimitotic and genotoxic effect of these secondary metabolites contained in the aqueous extract of the leaves of Peganum harmala L. by the Allium cepa L. test on meristematic cells by calculating the mitotic parameters (The mitotic index, the aberration index and the limit value of cytotoxicity).A spectrophotometric determination of secondary metabolites, namely alkaloids and flavonoids in the aqueous extract of this essence, was performed. As a result, the alkaloid content is estimated to be 28.42 μg EC/mg extract, and the flavonoid content is 12.52 μg EQ/mg extract. The determination of the mitotic index revealed disturbances in cell division with a highly significant difference between the negative control (distilled water) and the different samples (aqueous extracts, colchicine and quecetin). The exposure of meristematic cells to our samples resulted in a large number of chromosomal, nuclear and cellular aberrations with an aberration index reaching 16.21±1.28% for the 4mg/ml aqueous extract and 11.71±3.32% for the 10mg/ml aqueous extract. The limit value of cytotoxicity revealed that our samples are sublethal on Allium cepa L. meristematic cells.

Keywords: allium cepa l., antimitotic and genotoxic effect, aqueous leaf extract, laghouat (algeria), peganum harmala l., secondary metabolites

Procedia PDF Downloads 94
87 Efficient L-Xylulose Production Using Whole-Cell Biocatalyst With NAD+ Regeneration System Through Co-Expression of Xylitol Dehydrogenase and NADH Oxidase in Escherichia Coli

Authors: Mesfin Angaw Tesfay

Abstract:

L-Xylulose is a potentially valuable rare sugar used as starting material for antiviral and anticancer drug development in pharmaceutical industries. L-Xylulose exist in a very low concentration in nature and have to be synthesized from cheap starting materials such as xylitol through biotechnological approaches. In this study, cofactor engineering and deep eutectic solvent were applied to improve the efficiency of L-xylulose production from xylitol. A water-forming NAD+ regeneration enzyme (NADH oxidase) from Streptococcus mutans ATCC 25175 was introduced into E. coli with xylitol-4-dehydrogenase (XDH) of Pantoea ananatis resulting in recombinant cells harboring the vector pETDuet-xdh-SmNox. Further, three deep eutectic solvents (DES) including, Choline chloride/glycerol (ChCl/G), Choline chloride/urea (ChCl/U), and Choline chloride/ethylene glycol (ChCl/EG) have been employed to facilitate the conversion efficiency of L-xylulose from xylitol. The co-expression system exhibited optimal activity at a temperature of 37 ℃ and pH 8.5, and the addition of Mg2+ enhanced the catalytic activity by 1.19-fold. Co-expression of NADH oxidase with XDH enzyme resulted in increased L-xylulose concentration and productivity from xylitol as well as the intracellular NAD+ concentration. Two of the DES used (ChCl/U and ChCl/EG) show positive effects on product yield and the ChCl/G has inhibiting effects. The optimum concentration of ChCl/U was 2.5%, which increased the L-xylulose yields compared to the control without DES. In a 1 L fermenter the final concentration and productivity of L-xylulose from 50 g/L of xylitol reached 48.45 g/L, and 2.42 g/L.h respectively, which was the highest report. Overall, this study is a suitable approach for large-scale production of L-xylulose from xylitol using the engineered E. coli cell.

Keywords: Xylitol-4-dehydrogenase, NADH oxidase, L-xylulose, Xylitol, Coexpression, DESs

Procedia PDF Downloads 23
86 Expanding the Therapeutic Utility of Curcumin

Authors: Azza H. El-Medany, Hanan H. Hagar, Omnia A. Nayel, Jamila H. El-Medany

Abstract:

In search for drugs that can target cancer cell micro-environment in as much as being able to halt malignant cellular transformation, the natural dietary phytochemical curcumin was currently assessed in DMH-induced colorectal cancer rat model. The study enrolled 50 animals divided into a control group (n=10) and DMH-induced colorectal cancer control group (n=20) (20mg/kg-body weight for 28 weeks) versus curcumin-treated group (n=20) (160 mg/kg suspension daily oral for further 8 weeks). Treatment by curcumin succeeded to significantly decrease the percent of ACF and tended to normalize back the histological changes retrieved in adenomatous and stromal cells induced by DMH. The drug also significantly elevated GSH and significantly reduced most of the accompanying biochemical elevations (namely MDA, TNF-α, TGF-β and COX2) observed in colonic carcinomatous tissue, induced by DMH, thus succeeding to revert that of MDA, COX2 and TGF-β back to near normal as justified by being non-significantly altered as compared to normal controls. The only exception was PAF that was insignificantly altered by the drug. When taken together, it could be concluded that curcumin possess the potentiality to halt some of the orchestrated cross-talk between cancerous transformation and its micro-environmental niche that contributes to cancer initiation, progression and metastasis in this experimental cancer colon model. Envisioning these merits to a drug with already known safety preferentiality, awaits final results of current ongoing clinical trials, before curcumin can be added to the new therapeutic armamentarium of anticancer therapy.

Keywords: curcumin, dimethyl hydralazine, aberrant crypt foci, malondialdehyde, reduced glutathione, cyclooxygenase-2, tumour necrosis factor-alpha, transforming growth factor-beta, platelet activating factor

Procedia PDF Downloads 297
85 Isolation and Identification of Microorganisms from Marine-Associated Samples under Laboratory Conditions

Authors: Sameen Tariq, Saira Bano, Sayyada Ghufrana Nadeem

Abstract:

The Ocean, which covers over 70% of the world's surface, is wealthy in biodiversity as well as a rich wellspring of microorganisms with huge potential. The oceanic climate is home to an expansive scope of plants, creatures, and microorganisms. Marine microbial networks, which incorporate microscopic organisms, infections, and different microorganisms, enjoy different benefits in biotechnological processes. Samples were collected from marine environments, including soil and water samples, to cultivate the uncultured marine organisms by using Zobell’s medium, Sabouraud’s dextrose agar, and casein media for this purpose. Following isolation, we conduct microscopy and biochemical tests, including gelatin, starch, glucose, casein, catalase, and carbohydrate hydrolysis for further identification. The results show that more gram-positive and gram-negative bacteria. The isolation process of marine organisms is essential for understanding their ecological roles, unraveling their biological secrets, and harnessing their potential for various applications. Marine organisms exhibit remarkable adaptations to thrive in the diverse and challenging marine environment, offering vast potential for scientific, medical, and industrial applications. The isolation process plays a crucial role in unlocking the secrets of marine organisms, understanding their biological functions, and harnessing their valuable properties. They offer a rich source of bioactive compounds with pharmaceutical potential, including antibiotics, anticancer agents, and novel therapeutics. This study is an attempt to explore the diversity and dynamics related to marine microflora and their role in biofilm formation.

Keywords: marine microorganisms, ecosystem, fungi, biofilm, gram-positive, gram-negative

Procedia PDF Downloads 45
84 Involvement of BCRP/ABCG2 in Protective Mechanisms of Resveratrol against Methotrexate-Induced Renal Damage in Rats

Authors: Mohamed A. Morsy, Azza A. El-Sheikh, Abdulla Y. Al-Taher

Abstract:

Resveratrol (RES) is a well-known polyphenol antioxidant. We have previously shown that testicular protective effect of RES against the anticancer drug methotrexate (MTX)-induced toxicity involves transporter-mediated mechanisms. Here, we investigated the effect of RES on MTX-induced nephrotoxicity. Rats were administered RES (10 mg/kg/day) for 8 days, with or without a single MTX dose (20 mg/kg i.p.) at day 4 of the experiment. MTX induced nephrotoxicity evident by significantly increase in serum blood urea nitrogen and creatinine compared to control, as well as distortion of kidney microscopic structure. MTX also significantly increased renal nitric oxide level, with induction of inducible nitric oxide synthase expression. MTX also significantly up-regulated fas ligand and caspase 3. Administering RES prior to MTX significantly improved kidney function and microscopic picture, as well as significantly decreased nitrosative and apoptotic markers compared to MTX alone. RES, but not MTX, caused significant increase in expression of breast cancer resistance protein (BCRP), an apical efflux renal transporter that participates in urinary elimination of both MTX and RES. Interestingly, concomitant MTX and RES caused further up-regulation of renal Bcrp compared to RES alone. Using Human BCRP ATPase assay, both RES and MTX exhibited dose-dependent increase in ATPase activity, with Km values of 0.52 ± 0.03 and 30.9 ± 4.2 µM, respectively. Furthermore, combined RES and MTX caused ATPase activity which was significantly less than maximum ATPase activity attained by the positive control; sulfasalazine (12.5 µM). In conclusion, RES exerted nephro-protection against MTX-induced toxicity through anti-nitrosative and anti-apoptotic effects, as well as via up-regulation of renal Bcrp.

Keywords: methotrexate, resveratrol, nephrotoxicity, breast cancer resistance protein

Procedia PDF Downloads 295
83 Preparation of Flurbiprofen Derivative for Enhanced Brain Penetration

Authors: Jungkyun Im

Abstract:

Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective for relieving pain and reducing inflammation. They are nonselective inhibitors of two isoforms of COX, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), and thereby inhibiting the production of hormone-like lipid compounds such as, prostaglandins and thromboxanes which cause inflammation, pain, fever, platelet aggregation, etc. In addition, recently there are many research articles reporting the neuroprotective effect of NSAIDs in neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). However, the clinical use of NSAIDs in these diseases is limited by low brain distribution. Therefore, in order to assist the in-depth investigation on the pharmaceutical mechanism of flurbiprofen in neuroprotection and to make flurbiprofen a more potent drug to prevent or alleviate neurodegenerative diseases, delivery of flurbiprofen to brain should be effective and sufficient amount of flurbiprofen must penetrate the BBB thus gaining access into the patient’s brain. We have recently developed several types of guanidine-rich molecular carriers with high molecular weights and good water solubility that readily cross the blood-brain barrier (BBB) and display efficient distributions in the mouse brain. The G8 (having eight guanidine groups) molecular carrier based on D-sorbitol was found to be very effective in delivering anticancer drugs to a mouse brain. In the present study, employing the same molecular carrier, we prepared the flurbiprofen conjugate and studied its BBB permeation by mouse tissue distribution study. Flurbiprofen was attached to a molecular carrier with a fluorescein probe and multiple terminal guanidiniums. The conjugate was found to internalize into live cells and readily cross the BBB to enter the mouse brain. Our novel synthetic flurbiprofen conjugate will hopefully delivery NSAIDs into brain, and is therefore applicable to the neurodegenerative diseases treatment or prevention.

Keywords: flurbiprofen, drug delivery, molecular carrier, organic synthesis

Procedia PDF Downloads 231
82 Core-Shell Type Magnetic Nanoparticles for Targeted Drug Delivery

Authors: Yogita Patil-Sen

Abstract:

Magnetic nanoparticles such as those made of iron oxide have been widely explored as biocatalysts, contrast agents, and drug delivery systems. However, some of the challenges associated with these particles are agglomeration and biocompatibility, which lead to concern of toxicity of the particles, especially for drug delivery applications. Coating the particles with biocompatible materials such as lipids and peptides have shown to improve the mentioned issues. Thus, these core-shell type nanoparticles are emerging as the new class of nanomaterials for targeted drug delivery applications. In this study, various types of core-shell magnetic nanoparticles are prepared and characterized using techniques, such as Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Vibrating Sample Magnetometer (VSM) and Thermogravimetric Analysis (TGA). The heating ability of nanoparticles is tested under oscillating magnetic field. The efficacy of the nanoparticles as drug carrier is also investigated. The loading of an anticancer drug, Doxorubicin at 18 °C is measured up to 48 hours using UV-visible spectrophotometer. The drug release profile is obtained under thermal incubation condition at 37 °C and compared with that under the influence of oscillating field. The results suggest that the core-shell nanoparticles exhibit superparamagnetic behaviour, although, coating reduces the magnetic properties of the particles. Both the uncoated and coated particles show good heating ability, again it is observed that coating decreases the heating behaviour of the particles. However, coated particles show higher drug loading efficiency than the uncoated particles and the drug release is much more controlled under the oscillating magnetic field. Thus, the results strongly indicate the suitability of the prepared core-shell type nanoparticles as drug delivery vehicles and their potential in magnetic hyperthermia applications and for hyperthermia cancer therapy.

Keywords: core-shell, hyperthermia, magnetic nanoparticles, targeted drug delivery

Procedia PDF Downloads 336
81 Characterization, Antibacterial and Cytotoxicity Evaluation of Silver Nanoparticles Synthesised Using Grewia lasiocarpa E. Mey. Ex Harv. Plant Extracts

Authors: Nneka Augustina Akwu, Yougasphree Naidoo

Abstract:

Molecular advancement in technology has created a means whereby the atoms and molecules (solid forms) of certain materials such as plants, can now be reduced to a range of 1-100 nanometres. Green synthesis of silver nanoparticles (AgNPs) was carried out at room temperature (RT) 25 ± 2°C and 80°C, using the metabolites in the aqueous extracts of the leaves and stem bark of Grewia lasiocarpa as reductants and stabilizing agents. The biosynthesized AgNPs were characterized by UV-Vis spectrophotometry, attenuated total reflectance - Fourier transforms infrared (ATR-FTIR) spectroscopy, nanoparticle tracking analysis (NTA), Energy Dispersive X-ray fluorescence scanning electron microscope (SEM-EDXRF) and high-resolution transmission electron microscopy (HRTEM). The AgNPs were biologically evaluated for antioxidant, antibacterial and cytotoxicity activities. The phytochemical and FTIR analyses revealed the presence of metabolites that act as reducing and capping agents, while the UV-Vis spectroscopy of the biosynthesized NPs showed absorption between 380-460 nm, confirming AgNP synthesis. The Zeta potential values were between -9.1 and -20.6 mV with a hydrodynamics diameter ranging from 38.3 to 46.7 nm. SEM and HRTEM analyses revealed that AgNPs were predominately spherical with an average particle size of 2- 31 nm for the leaves and 5-27 nm for the stem bark. The cytotoxicity IC50 values of the AgNPs against HeLa, Caco-2 and MCF-7 were >1 mg/mL. The AgNPs were sensitive to all strains of bacteria used, with methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922) being more sensitive to the AgNPs. Our findings propose that antibacterial and anticancer agents could be derived from these AgNPs of G. lasiocarpa, and warrant their further investigation.

Keywords: antioxidant, cytotoxicity, Grewia lasiocarpa, silver nanoparticles, Zeta potentials

Procedia PDF Downloads 141
80 Empirical Measures to Enhance Germination Potential and Control Browning of Tissue Cultures of Andrographis paniculata

Authors: Nidhi Jindal, Ashok Chaudhury, Manisha Mangal

Abstract:

Andrographis paniculata, (Burm f.) Wallich ex. Nees (Family Acanthaceae) popularly known as King of Bitters, is an important medicinal herb. It has an astonishingly wide range of medicinal properties such as anti-inflammatory,antidiarrhoeal, antiviral, antimalarial, hepatoprotective, cardiovascular, anticancer, and immunostimulatory activities. It is widely cultivated in southern Asia. Though propagation of this herb generally occurs through seeds, it has many germination problems which intrigued scientists to work out on the alternative techniques for its mass production. The potential of tissue culture techniques as an alternative tool for AP multiplication was found to be promising. However, the high mortality rate of explants caused by phenolic browning of explants is one of the difficulties reported. Low multiplication rates were reported in the proliferation phase, as well as cultures decline characterized by leaf fall and loss of overall vigor. In view of above problems, a study was undertaken to overcome seed dormancy to improve germination potential and to investigate further on the possible means for successful proliferation of cultures via preventive approaches to overcome failures caused by phenolic browning. Experiments were conducted to improve germination potential and among all the chemical and mechanical trials, scarification of seeds with sand paper proved to be the best method to enhance the germination potential (82.44%) within 7 days. Similarly, several pretreatments and media combinations were tried to overcome browning of explants leading to the conclusion that addition of 0.1% citric acid and 0.2% of ascorbic acid in the media followed by rapid sub culturing of explants controlled browning and decline of explants by 67.45%.

Keywords: plant tissue culture, empirical measure, germination, tissue culture

Procedia PDF Downloads 414
79 Emerging Therapeutic Approach with Dandelion Phytochemicals in Breast Cancer Treatment

Authors: Angel Champion, Sadia Kanwal, Rafat Siddiqui

Abstract:

Harnessing phytochemicals from plant sources presents a novel opportunity to prevent or treat malignant diseases, including breast cancer. Chemotherapy lacks precision in targeting cancerous cells while sparing normal cells, but a phytopharmaceutical approach may offer a solution. Dandelion, a common weed plant, is rich in phytochemicals and provides a safer, more cost-effective alternative with lower toxicity than traditional pharmaceuticals for conditions such as breast cancer. In this study, an in-vitro experiment will be conducted using the ethanol extract of Dandelion on triple-negative MDA-231 breast cancer cell lines. The polyphenolic analysis revealed that the Dandelion extract, particularly from the root and leaf (both cut and sifted), had the most potent antioxidant properties and exhibited the most potent antioxidation activity from the powdered leaf extract. The extract exhibits prospective promising effects for inducing cell proliferation and apoptosis in breast cancer cells, highlighting its potential for targeted therapeutic interventions. Standardizing methods for Dandelion use is crucial for future clinical applications in cancer treatment. Combining plant-derived compounds with cancer nanotechnology holds the potential for effective strategies in battling malignant diseases. Utilizing liposomes as carriers for phytoconstituent anti-cancer agents offers improved solubility, bioavailability, immunoregulatory effects, advancing anticancer immune function, and reducing toxicity. This integrated approach of natural products and nanotechnology has significant potential to revolutionize healthcare globally, especially in underserved communities where herbal medicine is prevalent.

Keywords: apoptosis, antioxidant activity, cancer nanotechnology, phytopharmaceutical

Procedia PDF Downloads 54
78 Free Energy Computation of A G-Quadruplex-Ligand Structure: A Classical Molecular Dynamics and Metadynamics Simulation Study

Authors: Juan Antonio Mondragon Sanchez, Ruben Santamaria

Abstract:

The DNA G-quadruplex is a four-stranded DNA structure formed by stacked planes of four base paired guanines (G-quartet). Guanine rich DNA sequences appear in many sites of genomic DNA and can potential form G-quadruplexes, such as those occurring at 3'-terminus of the human telomeric DNA. The formation and stabilization of a G-quadruplex by small ligands at the telomeric region can inhibit the telomerase activity. In turn, the ligands can be used to down regulate oncogene expression making G-quadruplex an attractive target for anticancer therapy. Many G-quadruplex ligands have been proposed with a planar core to facilitate the pi–pi stacking and electrostatic interactions with the G-quartets. However, many drug candidates are impossibilitated to discriminate a G-quadruplex from a double helix DNA structure. In this context, it is important to investigate the site topology for the interaction of a G-quadruplex with a ligand. In this work, we determine the free energy surface of a G-quadruplex-ligand to study the binding modes of the G-quadruplex (TG4T) with the daunomycin (DM) drug. The complex TG4T-DM is studied using classical molecular dynamics in combination with metadynamics simulations. The metadynamics simulations permit an enhanced sampling of the conformational space with a modest computational cost and obtain free energy surfaces in terms of the collective variables (CV). The free energy surfaces of TG4T-DM exhibit other local minima, indicating the presence of additional binding modes of daunomycin that are not observed in short MD simulations without the metadynamics approach. The results are compared with similar calculations on a different structure (the mutated mu-G4T-DM where the 5' thymines on TG4T-DM have been deleted). The results should be of help to design new G-quadruplex drugs, and understand the differences in the recognition topology sites of the duplex and quadruplex DNA structures in their interaction with ligands.

Keywords: g-quadruplex, cancer, molecular dynamics, metadynamics

Procedia PDF Downloads 459
77 Anti-Oxidant and Anti-Cancer Activity of Helix aspersa Aqueous Extract

Authors: Ibtissem El Ouar, Cornelia Braicu, Dalila Naimi, Alexendru Irimie, Ioana Berindan-Neagoe

Abstract:

Helix aspersa, 'the garden snail' is a big land snail widely found in the Mediterranean countries, it is one of the most consumed species in the west of Algeria. It is commonly used in zootherapy to purify blood and to treat cardiovascular diseases and liver problems. The aim of our study is to investigate, the antitumor activity of an aqueous extract from Helix aspersa prepared by the traditional method on Hs578T; a triple negative breast cancer cell line. Firstly, the free radical scavenging activity of H. aspersa extract was assessed by measuring its capability for scavenging the radical 2,2-diphenyl-1-picrylhydrazyl (DPPH), as well as its ability to reduce ferric ion by the FRAP assay (ferric reducing ability). The cytotoxic effect of H. aspersa extract against Hs578T cells was evaluated by the MTT test (3-(4,5- dimethylthiazl-2-yl)-2,5- diphenyltetrazolium bromide)) while the mode of cell death induced by the extract has been determined by fluorescence microscopy using acredine orange/ethidium bromide (AO/EB) probe. The level of TNFα has also measured in cell medium by ELISA method. The results suggest that H. aspersa extract has an antioxidant activity, especially at high concentrations, it can reduce DPPH radical and ferric ion. The MTT test shows that H. aspersa extract has a great cytotoxic effect against breast cancer cells, the IC50 value correspond of the dilution 1% of the crude extract. Moreover, the AO/EB staining shows that TNFα induced necrosis is the main form of cell death induced by the extract. In conclusion, the present study may open new perspectives in the search for new natural anticancer drugs.

Keywords: breast cancer, Helix aspersa, Hs578t cell line, necrosis

Procedia PDF Downloads 422
76 In-silico Target Identification and Molecular Docking of Withaferin A and Withanolide D to Understand their Anticancer Therapeutic Potential

Authors: Devinder Kaur Sugga, Ekamdeep Kaur, Jaspreet Kaur, C. Rajesh, Preeti Rajesh, Harsimran Kaur

Abstract:

Withanolides are steroidal lactones and are highly oxygenated phytoconstituents that can be developed as potential anti-carcinogenic agents. The two main withanolides, namely Withaferin A and Withanolides D, have been extensively studied for their pharmacological activities. Both these withanolides are present in the Withania somnifera (WS) leaves belonging to the family Solanaceae, also known as “Indian ginseng .”In this study effects of WS leaf extract on the MCF7 breast cancer cell line were investigated by performing a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay to evaluate the cytotoxic effects and in vitro wound-healing assay to study the effect on cancer cell migration. Our data suggest WS extracts have cytotoxic effects and are effective anti-migrating agents and thus can be a source of potential candidates for the development of potential agents against metastasis. Thus, it can be a source of potential candidates for the development of potential agents against metastasis. Insight into these results, the in-silico approach to identify the possible protein targets interacting with withanolides was taken. Protein kinase C alpha (PKCα) was among the selected 5 top-ranked target proteins identified by the Swiss Target Prediction tool. PKCα is known to promote the growth and invasion of cancer cells and is being evaluated as a prognostic biomarker and therapeutic target in clinically aggressive tumors. Molecular docking of Withaferin A and Withanolides D was performed using AutoDock Vina. Both the bioactive compounds interacted with PKCα. The targets predicted using this approach will serve as leads for the possible therapeutic potential of withanolides, the bioactive ingredients of WS extracts, as anti-cancer drugs.

Keywords: withania somnifera, withaferin A, withanolides D, PKCα

Procedia PDF Downloads 146
75 Synthesis and Biological Activities of Novel -1,2,3-Triazoles Derivatives

Authors: Zahra Dehghani, Hoda Dehghani, Elham Zarenezhad

Abstract:

1,2,3-Triazole derivatives are important compounds in medicinal chemistry owing to their wide applications in drug discovery. They can readily associate with biologically targets through the hydrogen bonding and dipole interactions. The 1,2,3-triazole core is a key structural motif in many bioactive compounds, exhibiting a broad spectrum of biological activities, such as antiviral, anticancer, anti-HIV, antibiotic, antibacterial, and antimicrobial. Additionally, they have found significant industrial applications as dyes, agrochemicals, corrosion inhibitors, photo stabilizers, and photographic materials. we disclose the synthesis and characterization of 1-azido-3-(aryl-2-yloxy)propan-2-ol drivatives. The chemistry works well with various ß-azido alcohols involving aryloxy, alkoxy and alkyl residues, and also tolerates a wide spectrum of electron-donating and electron-withdrawing functional groups in both alkyne and azide molecules. Most of ß-azidoalcohols used in these experiments were pre-synthesized by the regioselective ring opening reaction of corresponded epoxides with sodium azide, whereas the majority of terminal alkynes were prepared via SN2-type reaction of propargyl bromide and corresponded nucleophiles. To evaluate the bioactivity of title compounds, the in vitro antifungal activity of all compound was investigated against several pathogenic fungi including Candida albicans, Candida krusei, Aspergillus niger, and Trichophyton rubrum , clotrimazole and fluconazole was used as standard antifungal drugs, also To understand the antibacterial activity of synthesized compounds, they were in vitro screened against E. coli and S. aureus as Gram-negative and Gram-positive bacteria, respectively. The in vitro tests have shown the promising antifungal but marginal antibacterial activity against tested fungi and bacteria.

Keywords: biological activities, antibacterial, antifungal, 1, 2, 3-Triazole

Procedia PDF Downloads 431
74 Evaluation of Naringenin Role in Inhibiton of Lung Tumor Progression in Mice

Authors: Vishnu Varthan Vaithiyalingamjagannathan, M. N. Sathishkumar, K. S. Lakhsmi, D. Satheeshkumar, Srividyaammayappanrajam

Abstract:

Background:Naringenin, aglycone flavonoid possess certain activities like anti-oxidant, anti-estrogenic, anti-diabetic, cardioprotective, anti-obesity,anti-inflammatory, hepatoprotective and also have anti-cancer characteristics like carcinogenic inactivation, cell cycle arrest, anti-proliferation, apoptosis, anti-angiogenesis and enhances anti-oxidant activity. Methodology:The inhibitory effect of Naringenin in lung tumor progression estimated with adenocarcinoma (A549) cell lines (in vitro) and C57BL/6 mice injected with 5 X 106A549 cell lines (in vivo) in a tri-dose manner (Naringenin 100mg/kg,150mg/kg, and 200mg/kg) compared with standard chemotherapy drug cisplatin (7mg/kg). Results:The results of the present study revealed a dose-dependent activity in Naringenin and combination with cisplatin at a higher dose which showed decreased tumor progression in mice. In vitro studies carried out for estimation of cell survival and Nitric Oxide (NO) level, shows dose dependent action of Naringenin with IC50 value of 42µg/ml. In vivo studies were carried out in C57BL/6 mice. Naringenin satisfied the condition of an anti-cancer molecule with its characteristics in fragmentation assay, Zymography assay, anti-oxidant, and myeloperoxidase studies, than cisplatin which failed in anti-oxidant and myeloperoxidase effect. Both in vitro and in vivo establishes dose dependent decrease in NO levels. But whereas, Naringenin showed adverse results in Matrix Metalloproteinase (MMP) enzymatic levels with increase in dose levels. Conclusion:From the present study, Naringenin could suppress the lung tumor progression when given individually and also in combinatorial with standard chemotherapy drug.

Keywords: naringenin, in vitro, cell line, anticancer

Procedia PDF Downloads 435
73 Natural Bio-Active Product from Marine Resources

Authors: S. Ahmed John

Abstract:

Marine forms-bacteria, actinobacteria, cynobacteria, fungi, microalgae, seaweeds mangroves and other halophytes an extremely important oceanic resources and constituting over 90% of the oceanic biomass. The marine natural products have lead to the discovery of many compounds considered worthy for clinical applications. The marine sources have the highest probability of yielding natural products. Natural derivatives play an important role to prevent the cancer incidences as synthetic drug transformation in mangrove. 28.12% of anticancer compound extracted from the mangroves. Exchocaria agollocha has the anti cancer compounds. The present investigation reveals the potential of the Exchocaria agollocha with biotechnological applications for anti cancer, antimicrobial drug discovery, environmental remediation, and developing new resources for the industrial process. The anti-cancer activity of Exchocaria agollocha was screened from 3.906 to 1000 µg/ml of concentration with the dilution leads to 1:1 to 1:128 following methanol and chloroform extracts. The cell viability in the Exchocaria agollocha was maximum at the lower concentration where as low at the higher concentration of methanol and chloroform extracts when compare to control. At 3.906 concentration, 85.32 and 81.96 of cell viability was found at 1:128 dilution of methanol and chloroform extracts respectively. At the concentration of 31.25 following 1:16 dilution, the cell viability was 65.55 in methanol and 45.55 in chloroform extracts. However, at the higher concentration, the cell viability 22.35 and 8.12 was recorded in the extracts of methanol and chloroform. The cell viability was more in methanol when compare to chloroform extracts at lower concentration. The present findings gives current trends in screening and the activity analysis of metabolites from mangrove resources and to expose the models to bring a new sustain for tackling cancer. Bioactive compounds of Exchocaria agollocha have extensive use in treatment of many diseases and serve as a compound and templates for synthetic modification.

Keywords: bio-active product, compounds, natural products and microalgae

Procedia PDF Downloads 246
72 Antimicrobial Activity of Endophytes on some Selected Clinical Isolates (Escherichia coli, Staphylococcus aureus, Salmonella Typhi, Bacillus subtilis, Klebsiella pneumoniae, Aspergillus fumigatus, Pseudomomonas aeruginosa and Penicillium chryysogenum)

Authors: Dawang D. N., Dasat G. S., Nden D.

Abstract:

Endophyte means “in the plant” are referred to all microorganisms that live in the internal tissues of stems, petioles, roots and leaves of plants causing no apparent symptoms of disease. Secondary metabolites from fungal endophytes have an enormous potential applications as antioxidant, antimicrobial, anticancer and antidiabeties. Thus, this study aimed to determine the antimicrobial activity of these metabolites against some clinical isolates. The fungi were subjected to fermentation medium and the metabolites were extracted using ethyl acetate. The fungal extracts showed both antibacterial and antifungal activities with maximum zone of inhibition diameter of 10.5mm against Aspergillus fumigatus. Staphylococcus aureus was inhibited by all the five crude extracts with inhibition zone diameter of 4mm. Endophytic fungal crude extract2 (EDF2) exhibited antimicrobial effect against all the test organisms used, EDF4 was active against all test organisms except on Penicillium chrysogenum and Klebsiella pneumoniae. Antibacterial standard of ciprofloxacin which is 15mm is comparable to the effect of endophytic extract of EDF1 and EDF2. Klebsiella pneumoniae was resistant to EDF4 and EDF5. EDF3 showed a wide range of antimicrobial activity against all the test organisms used. The highest inhibition zone diameter of 10.50mm recorded against Aspergillus fumigatus is comparable to antifungal standard of fluconazole (15.5mm). The result of this study suggests that endophytic fungi associated with the roots of Irish potato could be a promising source of novel bioactive compounds of pharmaceutical and industrial importance.

Keywords: endophyte, fungal extract, antimicrobial, potato

Procedia PDF Downloads 123
71 Effects of α-IFN –SingleWalled Carbon NanoTube and α-IFN-PLGA Encapsulated on Breast Cancer in Rats Induced by DMBA by Using CA15-3 Tumor Marker

Authors: Anoosh Eghdami

Abstract:

Background and aim: Conventional anticancer drugs display significant shortcomings which limit their use in cancer therapy. For this reason, important progress has been achieved in the field of nanotechnology to solve these problems and offer a promising and effective alternative for cancer treatment. Tumor markers may also be measured periodically during cancer therapy. Tumor markers may also be measured after treatment has ended to check for recurrence the return of cancer. The aim of this study was to evaluate the effect of nano drug delivery in induced breast cancer with DMBA by using CA15-3 tumor marker. Material and method: the rats were divided into five groups. The first group (control n=15) were fed only sesame oil as a gavage. In the second group n=15,10 mg DMBA was dissolved in 5ml of sesame oil and were fed as a gavage. In addition to DMBA treatment as the second group, in the 3,4and 5 groups after cancer creation, respectively affected by alpha interferon (α-IFN),alpha interferon conjugated with single walled carbon nano tube (α-IFN-SWNT) and encapsulated in poly lactic poly glycolic acid (α-IFN-PLGA). Tumor marker was measured in recent three groups. Results: The ANOVA test was used to determine the differences among the groups. Cancer inducing in rats (group 2) caused a significant increase in blood levels of CA15-3 (P<0.05). Administration of α-IFN, α-IFN –SWNT and α-IFN-PLGA in 3 groups of cancerous rats caused a significant decrease in blood levels of CA15-3 only the group that treated with α-IFN-PLGA (p<0.05). Conclusion: the results of this study indicate that nano drugs more effective than traditional drug in cancer treatment, although further work is needed to elucidate the safety and side effect of these compound in human.

Keywords: breast cancer, nano drug, tumor markers, CA15-3, α-IFN-PLGA, -IFN –SWNT

Procedia PDF Downloads 318