Search results for: PA1 ovarian cancer cell line

Authors: Hui-Hsin Huang, Sheng-Tung Huang, Chi-Ming Lee, Chiao-Han Yen, Chun-Mao Lin

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At initiation stage, there are no symptoms at initiation stage; however, at late stage, patients suffer symptoms as soon as ovarian cancer metastasis. Moreover, ovarian cancer cells are resistant to some anti-ovarian cancer drugs in clinical. Thus, it is very important to find an effective treatment for resistant ovarian cancer. Anthraquinone derivatives are able to induce DNA damage and lead to cell apoptosis, so several derivatives have been used for clinical application. Therefore, to explore more effective anti-ovarian cancer drugs, this study investigates the mechanism of three new anthraquinone compounds bearing different functional groups to camptothecin-resistance ovarian cell line A2780R2000. Cell viability was determined by MTT assay after treating A2780R2000 with the three new anthraquinone compounds. The results indicated that IC50 values are 33.44μM (Compound I), 25.77μM (Compound II) and 24.59μM (Compound III). Next, through cell cycle analysis, the results demonstrated that three new anthraquinone compounds not only induced A2780R2000 cell cycle arrest at early stage but also apoptosis at late stage. Besides, through apoptosis assay, the results indicated new anthraquinone compound induced apoptosis at late stage. Furthermore, the results of western blot show that the three new anthraquinone compounds lead to A2780R2000 apoptosis through intrinsic pathway. Theses results suggested that three new anthraquinone compounds may be potential new drugs for clinical cancer treatment in the future.

Keywords: anthraquinone, camptothecin, resistance, ovarian cancer

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Authors: Mashitoh Abd Rahman, Najihah Mohd Hashim, Faiqah Ramli, Syam Mohan, Noraziah Nordin, Hamed Karimian, Hapipah Mohd Ali

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Ovarian cancer is the most lethal gynecological malignancies. HME5, a prenylflavanoid has been isolated from local medicinal plant. This compound has been reported to possess a broad spectrum of biological activities including anticancer property. However, the potential of HME5 as an antiproliferative and cytotoxic agent on an ovarian cancer cells has not yet been investigated. In this present study, we examined the antiproliferative and cytotoxic effect of HME5 on Caov-3 (Human Ovarian Adenocarcinoma) cell line by using 3-[4,5-dimethylthizol-2-y]-2,5-diphenyltetrazolium bromide (MTT) assay, Acridine orange and propidium Iodide (AOPi) and cell cycle analysis study. HME5 has shown to inhibit Caov-3 in a time-dependent manner with the IC50 values of 5µg/ml, 2µg/ml and 1µg/ml after 24h, 48h and 72h treatment, respectively. Morphological study from AOPi analysis showed that HME5 induced apoptosis after 24 and 48h post-treatment. Nevertheless, HME5 exhibited cell cycle arrest at G1 phase as indicated in flow cytometry cell cycle profiling. In conclusion, HME5 inhibited proliferation of Caov-3 through induction of apoptosis and cell cycle arrest at G1 phase.

Keywords: apoptosis, prenylflavanoid, ovarian cancer, HME5

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Authors: M. Sunitha, B. Nithyavani, Mathew Yohannan, S. Thiruvieni Balajji, M. A. Rathi, C. Arul Raj, P. Ragavendran, V. K. Gopalkrishnan

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Establishment of an early and reliable biomarker for ovarian carcinogenesis whose expression can be monitored through noninvasive techniques will enable early diagnosis of cancer. Carbonic anhydrases (CA) isozymes IX and XII have been suggested to play a role in oncogenic processes. In von Hippel-Lindau (VHL)-defective tumors, the cell surface transmembrane carbonic anhydrase (CA) CA XI and CA XII genes are overexpressed because of the absence of pVHL. These enzymes are involved in causing a hypoxia condition, thereby providing an environment for metastasis. Aberrant expression of the facilitative glucose transporter GLUT I is found in a wide spectrum of epithelial malignancies. Studying the mRNA expression of CA IX, CA XII and Glut I isozymes in ovarian cancer cell lines (OAW-42 and PA-1) revealed the expression of these hypoxia genes. Immunohistochemical staining of carbonic anhydrases was also performed in 40 ovarian cancer tissues. CA IX and CA XII were expressed at 540 bp and 520 bp in OAW42, PA1 in ovarian cancer cell lines. GLUT-1 was expressed at 325bp in OAW 42, PA1 genes in ovarian cancer cell lines. Immunohistochemistry revealed high to moderate levels of expression of these enzymes. The immuostaining was seen predominantly on the cell surface membrane. The study concluded that these genes CA IX, CA XII and Glut I are expressed under hypoxic condition in tumor cells. From the present results expression of CA IX, XII and Glut I may represent potential targets in ovarian cancer therapy.

Keywords: ovarian cancer, carbonic anhydrase IX, XII, Glut I, tumor markers

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Authors: Patsorn Worawattananutai, Srisopa Ruangnoo, Arunporn Itharat

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Hibiscus sabdariffa (HS) leaves are vegetables which are extensively used as blood tonic and laxatives in Thai traditional medicine. They are popularly used as healthy sour soup for prevention of chronic diseases such as cancer. Therefore, the cytotoxic activity of different extracts of fresh and dried Hibiscus sabdariffa leaves were investigated via the sulforhodamine B (SRB) assay against three types of women’s cancer cell lines, namely the human cervical adenocarcinoma cell line (HeLa), the human ovarian adenocarcinoma cell line (SKOV-3), and the human breast adenocarcinoma cell line (MCF-7). Extraction methods were squeezing, boiling with water and maceration with 95% or 50% ethanol. The 95% ethanolic extracts of Hibiscus sabdariffa dry leaves (HSDE95) showed the highest cytotoxicity against all types of women’s cancer cell lines with the IC50 values in range 7.51±0.33 to 12.13±1.85 µg/ml. Its IC50 values against SKOV-3, HeLa and MCF-7 were 7.51±0.33, 9.44±1.41 and 12.13±1.85 µg/ml, respectively. In these results, this extract can be classified as “active” according to the NCI guideline which indicated that IC50 values of the active cytotoxic plant extracts have to be beneath 20 µg/ml. Thus, HSDE95 was concluded to be a potent cytotoxic drug for all women’s cancer cells. This extract should be further investigated to isolate active compounds against women’s cancer cells.

Keywords: breast adenocarcinoma, cervical adenocarcinoma, cytotoxic activity, Hibiscus sabdariffa, ovarian adenocarcinoma

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Authors: I. Ramalho, S. Campos, M. Dias

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Introduction: Endometriosis may play a role in the pathogenesis of ovarian cancer (OC), however, the risk and prognosis have not been well established. The association between these two pathologies could have an important impact on prevention and early diagnosis of OC. Objective: To analyze the prevalence of endometriosis associated ovarian cancer and related clinical, epidemiological and histopathological issues. Design: We conducted a retrospective case series analysis of patients diagnosed with endometriosis and ovarian cancer in the Gynecology Department of Coimbra University Hospital Center since 2006 to 2015. Methods: We collected data from women diagnosed with ovarian cancer, with anatomopathology records reporting findings of endometriosis in ovarian cancer patients. Patients were retrieved from the pathological records and appropriate medical records were retrospectively reviewed. Statistical analysis was performed using SPSS 22.0. Results: Histological evidence of endometriosis was found in 17 out of 261 patients diagnosed with ovarian cancer (OC) (6.51%). The most usual symptoms were pelvic pain, abdominal distension, asthenia, ascites, weight loss and nausea. Mean age at diagnosis was 61.2 ± 15.1, 41-86 years old, 33.3% were pre-menopausal patients and cancer stage distribution was predominantly stage I (31.3%) and stage III (56.3%). OC occurred unilaterally in 14 patients and 2 patients were diagnosed with a synchronous ovarian and endometrial cancer. Regarding histological type, 10 OC were classified as clear cell carcinoma (CCC), 4 endometrioid carcinomas (EC) and 3 mixed type (clear cell and endometrioid). Four ovarian carcinomas presumably arose from endometriomas: 3 CCC and 1 EC. Conclusions: In accordance with previous studies, clear cell was the most common pathological type in endometriotic patients, followed by endometrioid carcinomas, and two rare synchronous ovarian and endometrial carcinomas were registered. Although endometriosis association to OC is uncommon, endometriosis should be managed with special care in order to early diagnosis.

Keywords: endometriosis, histology, observational study, ovarian cancer

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

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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

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Authors: Merry Meryam Martgrita, Marselina Irasonia Tan

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One of several aggresive cancer is cancer that overexpress c-erbB2 receptor along with the expression of estrogen receptor. Components of extracellular matrix play an important role to increase cancer cells proliferation, migration and invasion. Both components can affect cancer development by regulating the signal transduction pathways in cancer cells. In recent research, SKOV-3 ovarian cancer cell line, that overexpress c-erbB2 receptor was cultured on type IV collagen and treated with estradiol-17β, to reveal the role of both components on RNA and protein level of c-erbB2 receptor. In this research we found a modulation phenomena of increasing and decreasing of c-erbB2 RNA level and a stabilisation phenomena of c-erbB2 protein expression due to estradiol-17β and type IV collagen. It seemed that estradiol-17β has an important role to increase c-erbB2 transcription and the stability of c-erbB2 protein expression. Type IV collagen has an opposite role. It blocked c-erbB2 transcription when it bound to integrin receptor in SKOV-3 cells.

Keywords: c-erbB2, estradiol-17β, SKOV-3, type IV collagen

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Authors: Noor Shafifiyaz Mohd Yazid, Najihah Mohd Hashim, Hapipah Mohd Ali, Syam Mohan, Rosea Go

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Artocarpus kemando is a plant species from Moraceae family. This plant is used as household utensil by the local and the fruits are edible. The plants’ bark was used for the extraction process and yielded the chloroform crude extract which was used to screen for anticancer potential. The cytotoxic effect of the extract on CAOV-3 and WRL 68 cell lines were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide or MTT assays. Qualitative AO/PI assay was performed to confirm the apoptosis and necrosis process. 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. In MTT assay, A. kemando inhibited 50% growth of CAOV-3 cells at 27.9 ± 0:03, 20.1± 0:03, 18.21± 0:04 µg/mL after 24, 48 and 72 hour, respectively. The morphology changes can be seen on CAOV-3 with a production of cell membrane blebbing, cromatin condensation and apoptotic bodies. Evaluation of cytotoxicity 3 on CAOV-3 cells after treated with extract resulting loss of mitochondrial membrane potential and release of cytochrome c from mitochondria. The results demonstrated A. kemando has potentially anticancer agent, particularly on human ovarian cancer.

Keywords: anticancer, Artocarpus kemando, ovarian cancer, cytotoxicity

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Authors: Radia Chemlal, Salim Mehenni, Dahbia Leila Anes-boulahbal, Mohamed Kherat, Nabil Mameri

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The application of the electric field is considered to be a very promising method in cancer therapy. Indeed, cancer cells are very sensitive to the electric field, although the cellular response is not entirely clear. The tests carried out consisted in subjecting the RD cell line under the effect of the continuous electric field while varying certain parameters (voltage, exposure time, and cell concentration). The response surface methodology (RSM) was used to assess the effect of the chosen parameters, as well as the existence of interactions between them. The results obtained showed that the voltage, the cell concentration as well as the interaction between voltage and exposure time have an influence on the mortality rate of the RD cell line.

Keywords: continuous electric field, RD cancer cell line, RSM, voltage

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Authors: Hirowati Ali, Aisyah Ellyanti, Dewi Rusnita, Septelia Inawati Wanandi

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Stem cell has been known for its potency to be differentiated in many cells. Recently stem cell has been used for many treatment of degenerative medicine. It is still controversy whether stem cell can be used for therapy or these cells can activate cancer stem cell. SCUBE2 is a novel secreted and membrane-anchored protein which has been reported to its role in better prognosis and inhibition of cancer cell proliferation. Our study aims to observe whether stem cell can up-regulate SCUBE2 gene in MCF7 breast cancer cell line. We used in vitro study using MCF-7 cell treated with stem cell derived from placenta Wharton's jelly which has been known for its stemness and widely used. Our results showed that MCF-7 cell line grows up rapidly in 6-well culture dish. Stem cell was cultured in 6-well dish. After 50%-60% MCF-7 confluence, we co-cultured these cells with stem cells for 24 hours and 48 hours. We hypothesize SCUBE2 gene which is previously known for its higher expression in better prognosis of breast cancer, is up-regulated after stem cells addition in MCF7 culture dishes.

Keywords: breast cancer cells, inhibition of cancer cells, mesenchymal stem cells, SCUBE2

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Authors: K. Suresh, R. Arunkumar

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The objective of this study is to investigate the preparation of gramine nano suspension and protective effect of Gramine on the apoptosis of laryngeal cancer cells cell line (HEp-2 and KB). The growth inhibition rate of Hep-2 and KB cells in vitro were measured by MTT assay and apoptosis by, levels of reactive oxygen species, mitochondrial membrane potential, morphological changes and flowcytometry. Based on the results, we determined the effective doses of gramine as 127.23µm/ml for 24 hr and 119.81 µm/ml for 48hr in hep-2 cell line and 147.58 µm ml for 24 hr and 123.74µm µm/ml for 48hr in KB cell line. cytotoxicity effects of gramine were confirmed by treatment of HEp-2 cell and KB cell with IC50 concentration of gramine resulted in sequences of events marked by the enhance the apoptosis accompanied by loss of cell viability, modulation of reactive oxygen species and cell cycle arrest through the induction of G0/G1 phase arrest on HEp-2 cells. Our study suggests that the nanosuspension of gramine possesses the more cytotoxic effect of cancer cells and a novel candidate for cancer chemoprevention.

Keywords: apoptosis, HEp-2 cell line, KB cell line mitochondria, gramine, nanosuspension

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Authors: Amar Ranjan, Julieana Durai, Pranay Tanwar

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Background &Introduction: Ovarian cancer is one of the most common malignant tumor in the female. 70% of the cases of ovarian cancer are diagnosed at an advanced stage. The five-year survival rate associated with ovarian cancer is less than 30%. The early diagnosis of ovarian cancer becomes a key factor in improving the survival rate of patients. Presently, CAl25 (carbohydrate antigen125) is used for the diagnosis and therapeutic monitoring of ovarian cancer, but its sensitivity and specificity is not ideal. The introduction of HE4, human epididymis protein 4 has attracted much attention. HE4 has a sensitivity and specificity of 72.9% and 95% for differentiating between benign and malignant adnexal masses, which is better than CA125 detection.  Methods: Serum HE4 and CA -125 were estimated using the chemiluminescence method. Our cases were 40 epithelial ovarian cancer, 9 benign ovarian tumor, 29 benign gynaecological diseases and 13 healthy individuals. This group include healthy woman those who have undergoing family planning and menopause-related medical consultations and they are negative for ovarian mass. Optimal cut off values for HE4 and CA125 were 55.89pmol/L and 40.25U/L respectively (determined by statistical analysis). Results: The level of HE4 was raised in all ovarian cancer patients (n=40) whereas CA125 levels were normal in 6/40 ovarian cancer patients, which were the cases of OC confirmed by histopathology. There is a significant decrease in the level of HE4 with comparison to CA125 in benign ovarian tumor cases. Both the levels of HE4 and CA125 were raised in the nonovarian cancer group, which includes cancer of endometrium and cervix. In the healthy group, HE4 was normal in all patients except in one case of the rudimentary horn, and the reason for this raised HE4 level is due to the incomplete development of uterus whereas CA125 was raised in 3 cases. Conclusions: Findings showed that the serum level of HE4 is an important indicator in the diagnosis of ovarian cancer, and it also distinguishes between benign and malignant pelvic masses. However, a combination of HE4 and CA125 panel will be extremely valuable in improving the diagnostic efficiency of ovarian cancer. These findings of our study need to be validated in the larger cohort of patients.

Keywords: human epididymis protein 4, ovarian cancer, diagnosis, benign lesions

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Authors: Salma Baig, Bakrudeen Ali Ahmad, Ainnul Hamidah Syahadah Azizan, Hapipah Mohd Ali, Elham Rouhollahi, Mahmood Ameen Abdulla

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Free radical damage induced by reactive oxygen species (ROS) contributes to etiology of many chronic diseases, cancer being one of them. Recent studies have been successful in ROS targeted therapies via antioxidants using mouse models in cancer therapeutics. The present study was designed to scrutinize anticancer activity, antioxidant activity of 5 different extracts of Thymus serpyllum in MDA-MB-231, MCF-7, HepG2, HCT-116, PC3, and A549. Identification of the phytochemicals present in the most active extract of Thymus serpyllum was conducted using gas chromatography coupled with mass spectrophotometry and antioxidant activity was measured by using DPPH radical scavenging and FRAP assay. Anticancer impact of the extract in terms of IC50 was evaluated using MTT cell viability assay. Results revealed that the hexane extract showed the best anticancer activity in HepG2 (Liver Carcinoma Cell Line) with an IC50 value of 23 ± 0.14 µg/ml followed by 25 µg/ml in HCT-116 (Colon Cancer Cell Line), 30 µm/ml in MCF-7 (Breast Cancer Cell Line), 35 µg/ml in MDA-MB-231 (Breast Cancer Cell Line), 57 µg/ml in PC3 (Prostate Cancer Cell Line) and 60 µg/ml in A549 (Lung Carcinoma Cell Line). GC-MS profile of the hexane extract showed the presence of 31 compounds with carvacrol, thymol and thymoquione being the major compounds. Phenolics such as Vitamin E, terpinen-4-ol, borneol and phytol were also identified. Hence, here we present the first report on cytotoxicity of hexane extract of Thymus serpyllum extract in HepG2 cell line with a robust anticancer activity with an IC50 of 23 ± 0.14 µg/ml.

Keywords: Thymus serpyllum L., hexane extract, GC-MS profile, antioxidant activity, anticancer activity, HepG2 cell line

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Authors: Drashti G. Daraji, Rosa E. Moo-Puc, Hitesh D. Patel

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Substituted 2-Thioimidazole analogues have been synthesized and confirmed by advanced spectroscopic techniques. Among them, ten compounds have been selected and evaluated for their in vitro anti-cancer activity at the National Cancer Institute (NCI) for testing against a panel of 60 different human tumor cell lines derived from nine neoplastic cancer types. Furthermore, synthesized compounds were tested for their in vitro antiprotozoal activity, and none of them exhibited significant potency against antiprotozoans. It was observed that the tested all compounds seem effective on the UACC-62 melanoma cancer cell line as compared to other cancer cell lines and also exhibited the least potent in the Non-Small Cell Lung Cancer cell line in one-dose screening. In silico studies of these derivatives were carried out by molecular docking techniques and Absorption, Distribution, Metabolism, and Excretion (ADME) using Schrödinger software to find potent B-Raf kinase inhibitor (PDB ID: 3OG7). All the compounds have been performed for docking study; Compound D4 has a good docking score for melanoma cancer as compared with other.

Keywords: anticancer activity, cancer cell line, 2-thio imidazole, one-dose assay, molecular docking

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Authors: Zakaria Baka, Halima Alem

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Cancer is a major worldwide health problem that has caused around ten million deaths in 2020. In addition, efforts to develop new anti-cancer drugs still face a high failure rate. This is partly due to the lack of preclinical models that recapitulate in-vivo drug responses. Indeed conventional cell culture approach (known as 2D cell culture) is far from reproducing the complex, dynamic and three-dimensional environment of tumors. To set up more in-vivo-like cancer models, 3D bioprinting seems to be a promising technology due to its ability to achieve 3D scaffolds containing different cell types with controlled distribution and precise architecture. Moreover, the introduction of microfluidic technology makes it possible to simulate in-vivo dynamic conditions through the so-called “cancer-on-chip” platforms. Whereas several cancer types have been modeled through the cancer-on-chip approach, such as lung cancer and breast cancer, only a few works describing ovarian cancer models have been described. The aim of this work is to combine 3D bioprinting and microfluidic technics with setting up a 3D dynamic model of ovarian cancer. In the first phase, alginate-gelatin hydrogel containing SKOV3 cells was used to achieve tumor-like structures through an extrusion-based bioprinter. The desired form of the tumor-like mass was first designed on 3D CAD software. The hydrogel composition was then optimized for ensuring good and reproducible printability. Cell viability in the bioprinted structures was assessed using Live/Dead assay and WST1 assay. In the second phase, these bioprinted structures will be included in a microfluidic device that allows simultaneous testing of different drug concentrations. This microfluidic dispositive was first designed through computational fluid dynamics (CFD) simulations for fixing its precise dimensions. It was then be manufactured through a molding method based on a 3D printed template. To confirm the results of CFD simulations, doxorubicin (DOX) solutions were perfused through the dispositive and DOX concentration in each culture chamber was determined. Once completely characterized, this model will be used to assess the efficacy of anti-cancer nanoparticles developed in the Jean Lamour institute.

Keywords: 3D bioprinting, ovarian cancer, cancer-on-chip models, microfluidic techniques

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Authors: Salina Yahya Saddick

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Ovarian cancer remains the most lethal gynecological malignancy due to the lack of highly sensitive and specific screening tools for detection of early-stage disease. The OSE provides the progenitor cells for 90% of human ovarian cancers. Recent morphologic, immunohistochemical and molecular genetic studies have led to the development of a new paradigm for the pathogenesis and origin of epithelial ovarian cancer (EOC) based on a ualistic model of carcinogenesis that divides EOC into two broad categories designated Types I and II which are characterized by specific mutations, including KRAS, BRAF, ERBB2, CTNNB1, PTEN PIK3CA, ARID1A, and PPPR1A, which target specific cell signaling pathways. Type 1 tumors rarely harbor TP53. type I tumors are relatively genetically stable and typically display a variety of somatic sequence mutations that include KRAS, BRAF, PTEN, PIK3CA CTNNB1 (the gene encoding beta catenin), ARID1A and PPP2R1A but very rarely TP53 . The cancer stem cell (CSC) hypothesis postulates that the tumorigenic potential of CSCs is confined to a very small subset of tumor cells and is defined by their ability to self-renew and differentiate leading to the formation of a tumor mass. Potential protein biomarker miRNA, are promising biomarkers as they are remarkably stable to allow isolation and analysis from tissues and from blood in which they can be found as free circulating nucleic acids and in mononuclear cells. Recently, genomic anaylsis have identified biomarkers and potential therapeutic targets for ovarian cancer namely, FGF18 which plays an active role in controlling migration, invasion, and tumorigenicity of ovarian cancer cells through NF-κB activation, which increased the production of oncogenic cytokines and chemokines. This review summarizes update information on epithelial ovarian cancers and point out to the most recent ongoing research.

Keywords: epithelial ovarian cancers, somatic sequence mutations, cancer stem cell (CSC), potential protein, biomarker, genomic analysis, FGF18 biomarker

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Authors: H. Tayefih, F. farajzade ahari, F. Zarghami, V. Zeighamian, N. Zarghami, Y. Pilehvar-soltanahmadi

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Breast cancer is the most frequently occurring cancer among women throughout the world. Natural compounds such as curcumin hold promise to treat a variety of cancers including breast cancer. However, curcumin's therapeutic application is limited, due to its rapid degradation and poor aqueous solubility. On the other hand, previous studies have stated that drug delivery using nanoparticles might improve the therapeutic response to anticancer drugs. Poly (N-isopropylacrylamide-co-methacrylic acid) (PNIPAAm–MAA) is one of the hydrogel copolymers utilized in the drug delivery system for cancer therapy. The aim of this study was to examine the cytotoxic potential of curcumin encapsulated within the NIPAAm-MAA nanoparticle, on the MCF-7 breast cancer cell line. In this work, polymeric nanoparticles were synthesized through the free radical mechanism, and curcumin was encapsulated into NIPAAm-MAA nanoparticles. Then, the cytotoxic effect of curcumin-loaded NIPAAm-MAA on the MCF-7 breast cancer cell line was measured by MTT assays. The evaluation of the results showed that curcumin-loaded NIPAAm-MAA has more cytotoxic effect on the MCF-7 cell line and efficiently inhibited the growth of the breast cancer cell population, compared with free curcumin. In conclusion, this study indicates that curcumin-loaded NIPAAm-MAA suppresses the growth of the MCF-7 cell line. Overall, it is concluded that encapsulating curcumin into the NIPAAm-MAA copolymer could open up new avenues for breast cancer treatment.

Keywords: PNIPAAm-MAA, breast cancer, curcumin, drug delivery

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Authors: Kamta P. Namdeo

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Novel thiazolidino-(3,2-b)-1, 2,4-triazole-5(6H)-one derivatives were synthesized, and anticancer activity was studied on human breast cancer cell line MFC7. It showed a significant decrease in cell viability with reference to the standard. The findings suggest that nitro-substituted compound showed best anticancer activity and activity was due to the triazole and thiazolidinone hetero nucleus present in the structure.

Keywords: anti-cancer, adriamycine, thiazolidinone, 1, 2, 4-triazole, thiazolidino-triazolone

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Authors: Anushaa A.

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In this work, silver nanoparticles (AgNP) were manufactured directly without harmful chemicals utilising methanol extract (SNLME) Solanum nigrume leaves. We are using nigrum leaf extract from Solanum, which converts silver nitrate to silver ions, for synthesization purposes. An examination of the AgNP produced was performed using ultraviolet (UV-VIS) spectroscopy, infrared spectroscopy (FTIR) transformed from Fourier and scanning electrons (SEM). Biological activity was also tested. UV-VIS has proven that biosynthesized AgNP exists (420-450 nm). The FTIR spectrum has been utilised to confirm the presence of different functional groups within the biomolecules, which are a nanoparticular capping agent and the spectroscopic and crystal nature of AgNP. The viability of the silver nanoparticles was evaluated using zeta potential calculations. Negative zeta potential of -33.4 mV demonstrated the stability of silver-nanoparticles. The morphology of AgNP was examined using a scanning electron microscope. Greenly generated AgNP showed significant anti-Staphylococcus aureus, Candida, and Escherichia coli action. The green AgNP demonstration indicated that the IC50 for the human teratocarcinoma cell line was 29.24 μg/ml during 24 hours of therapy (PA1 Ovarian cell line). The dose-dependent effects were reported in both antibacterial and cytotoxicity assays and as an effective agent. Finally, the findings of this research showed that silver nanoparticles generated might serve as a viable therapeutic agent to combat microorganisms killing and curing cancer.

Keywords: antimicrobial activity, PA1 ovarian cancer cell line, silver nanoparticles, Solanum nigrum

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Authors: Salma Mirza, Syeda Asma Naqvi, Khalid Mohammed Khan, M. Iqbal Choudhary

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In this study twenty-five (25) newly synthesized compounds substituted aryl thiazoles (SAT) 1-25 were synthesized, and in vitro cytotoxicity of these compounds was evaluated against four cancer cell lines namely, MCF-7 (ER+ve breast), MDA-MB-231 (ER-ve breast), HCT116 (colorectal), and, HeLa (cervical) and compared with the standard anticancer drug doxorubicin with IC50 value of 1.56 ± 0.05 μM. Among them, compounds 1, 4-8 and 19 were found to be active against all four cell lines. Compound 20 was found to be selectively active against MCF7 cells with IC50 value of 40.21 ± 4.15 µM, whereas compound 19 was active against only MCF7 and HeLa cells with IC50 values of 46.72 ± 1.8 and 19.86 ± 0.11 μM, respectively. These results suggest that aryl thiazoles 1 and 4 deserve to be investigated further in vivo as anti-cancer agents.

Keywords: anticancer agents, breast cancer cell lines (MCF7, MDA-MB-231), colorectal cancer cell line (HCT-116), cervical cancer cell line (HeLa), Thiazole derivatives

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Authors: Aliaa M. Issa, Mahmoud N. ElRouby, Sahar A. S. Ahmad, Mahmoud M. El-Merzabani

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Sider honey is a type of honey produced by bees feeding on the nectar of Sider tree, Ziziphus spina-christi (L) Desf . Honey is an effective agent for preventing, inhibiting and treating the growth of human and animal cancer cell lines in vitro and in vivo. The aim of the present study was to evaluate the impact of different dilutions from crude Sider honey and different duration times of exposure on the growth of six tumor cell lines (human cervical cancer cell line, HeLa; human hepatocellular carcinoma cell line, HepG-2; human larynx carcinoma cell line, Hep-2; brain tumor cell line, U251) as well as one animal cancerous cell line (Ehrlich ascites carcinoma cells line, EAC) and one normal cell line, Homo sapiens, human, (WISH) CCL-25. Different concentrations and treatment durations with Sider honey were tested on the growth of several cancer cell lines types. Histopathological changes in the tumor masses, animal survival, apoptosis and necrosis of the used cancer cell lines (using flow cytometry) were evaluated. Sider honey was administers either to the tumor mass itself by intratumoral injection or via drinking water. One-way ANOVA test was used for the analysis of (the means + standard error) of the optical density obtained from the Elisa reader and flow cytometry. The study revealed that different concentrations of Sider honey affected the growth patterns of all the studied cancer cell lines as well as their histopathological changes, and it depended on the cell line nature and the concentration of honey used. It is obvious that the relative animal survival percentage (bearing Ehrlich ascites carcinoma, EAC cells) was proportionally increased with the increase in the used honey concentrations. The study of apoptosis and necrosis using the flow cytometry technique emphasized the viability results. In conclusion, Sider honey was effective as antitumor agent, in the used concentrations.

Keywords: antitumor, honey, sider, tumor cell lines

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Authors: AliAkbar Hafezi, Jahanbakhsh Asadi, Majid Shahbazi, Alijan Tabarraei, Nader Mansour Samaei, Hamed Sheibak, Roghaye Gharaei

Abstract:

Background: Breast cancer is the most common cancer in women. In most cancer cells, apoptosis is blocked. As for the importance of apoptosis in cancer cell death and the role of different genes in its induction or inhibition, the search for compounds that can begin the process of apoptosis in tumor cells is discussed as a new strategy in anticancer drug discovery. The aim of this study was to investigate the effect of Naringenin (NGEN) on the apoptosis in the T47D cell line of breast cancer. Materials and Methods: In this experimental study in vitro, the T47D cell line of breast cancer was selected as a sample. The cells at 24, 48, and 72 hours were treated with doses of 20, 200, and 1000 µm of Naringenin. Then, the transcription levels of the genes involved in apoptosis, including Bcl-2, Bax, Caspase 3, Caspase 8, Caspase 9, P53, PARP-1, and FAS, were assessed using Real Time-PCR. The collected data were analyzed using IBM SPSS Statistics 24.0. Results: The results showed that Naringenin at doses of 20, 200, and 1000 µm in all three times of 24, 48, and 72 hours increased the expression of Caspase 3, P53, PARP-1 and FAS and reduced the expression of Bcl-2 and increased the Bax/Bcl-2 ratio, nevertheless in none of the studied doses and times, had not a significant effect on the expression of Bax, Caspase 8 and Caspase 9. Conclusion: This study indicates that Naringenin can reduce the growth of some cancer cells and cause their deaths through increased apoptosis and decreased anti-apoptotic Bcl-2 gene expression and, resulting in the induction of apoptosis via both internal and external pathways.

Keywords: apoptosis, breast cancer, naringenin, T47D cell line

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Authors: Y. Pilehvar-Soltanahmadi, F. Badrzadeh, N. Zarghami, S. Jalilzadeh-Tabrizi, R. Zamani

Abstract:

Herbal compounds such as curcumin which decrease telomerase and gene expression have been considered as beneficial tools for lung cancer treatment. In this article, we compared the effects of pure curcumin and curcumin-loaded NIPAAm-MAA nanoparticles on telomerase and PinX1 gene expression in a lung cancer cell line. A tetrazolium-based assay was used for determination of cytotoxic effects of curcumin on the Calu-6 lung cancer cell line and telomerase and pinX1 gene expression was measured with real-time PCR. MTT assay showed that Curcumin-loaded NIPAAm-MAA inhibited the growth of the Calu-6 lung cancer cell line in a time and dose-dependent manner. Our q-PCR results showed that the expression of telomerase gene was effectively reduced as the concentration of curcumin-loaded NIPAAm-MAA increased while expression of the PinX1 gene became elevated. The results showed that curcumin loaded NIPAAm-MAA exerted cytotoxic effects on the Calu-6 cell line through down-regulation of telomerase and stimulation of pinX1 gene expression. NIPPAm-MAA could be the good carrier for such kinds of hydrophobic agent.

Keywords: curcumin, NIPAAm-MAA, PinX1, telomerase, lung cancer cells

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Authors: Adel Alblihy, Reem Ali, Mashael Algethami, Ahmed Shoqafi, Michael S. Toss, Juliette Brownlie, Natalie J. Tatum, Ian Hickson, Paloma Ordonez Moran, Anna Grabowska, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan

Abstract:

Platinum resistance is a clinical challenge in ovarian cancer. Platinating agents induce DNA damage which activate Mre11 nuclease directed DNA damage signalling and response (DDR). Upregulation of DDR may promote chemotherapy resistance. Here we have comprehensively evaluated Mre11 in epithelial ovarian cancers. In clinical cohort that received platinum- based chemotherapy (n=331), Mre11 protein overexpression was associated with aggressive phenotype and poor progression free survival (PFS) (p=0.002). In the ovarian cancer genome atlas (TCGA) cohort (n=498), Mre11 gene amplification was observed in a subset of serous tumours (5%) which correlated highly with Mre11 mRNA levels (p<0.0001). Altered Mre11 levels was linked with genome wide alterations that can influence platinum sensitivity. At the transcriptomic level (n=1259), Mre11 overexpression was associated with poor PFS (p=0.003). ROC analysis showed an area under the curve (AUC) of 0.642 for response to platinum-based chemotherapy. Pre-clinically, Mre11 depletion by gene knock down or blockade by small molecule inhibitor (Mirin) reversed platinum resistance in ovarian cancer cells and in 3D spheroid models. Importantly, Mre11 inhibition was synthetically lethal in platinum sensitive XRCC1 deficient ovarian cancer cells and 3D-spheroids. Selective cytotoxicity was associated with DNA double strand break (DSB) accumulation, S-phase cell cycle arrest and increased apoptosis. We conclude that pharmaceutical development of Mre11 inhibitors is a viable clinical strategy for platinum sensitization and synthetic lethality in ovarian cancer.

Keywords: MRE11; XRCC1, ovarian cancer, platinum sensitization, synthetic lethality

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Authors: Ghada Esheba, Ghadeer Aldoobi, Salwa Almalk, Abrar Alshareef, Eman Al-khairi, Eman Yaseen

Abstract:

Background: In Saudi Arabia, ovarian cancer ranked seventh among female population and is the most common female genital tract malignancy after endometrial cancer. A slight increase in the incidence of ovarian cancer was observed from 2001–2008. Makkah, Riyadh, and the eastern region of Saudi Arabia had the highest incidence rate ratio for the number of ovarian cancer cases (1). Differentiating metastatic adenocarcinomas from primary ovarian carcinomas, especially those of endometrioid and mucinous type is clinically significant and a challenge for clinicians and pathologists, yet the distinction has important therapeutic and prognostic implications. Aim: To clarify the most important histopathological criteria to differentiate between primary ovarian surface epithelial tumors especially mucinous and endometrioid subtypes, and metastatic adenocarcinoma and to evaluate the value of a panel of antibodies consisting of CK7, CK20, and CDX-2 in the distinction between primary ovarian surface epithelial tumors and metastatic adenocarcinoma. Material and methods: This study was carried out on 26 cases of primary ovarian surface epithelial neoplasms and 14 cases of metastatic ovarian adenocarcinoma. All cases were studied immunohistochemically using CK7, CK20, and CDX-2. Results: All cases of primary ovarian adenocarcinoma were positive for CK7. 25% and 58% of mucinous borderline mucinous tumor and mucinous carcinoma respectively were positive for CK20. Only 42% of mucinous carcinoma were positive for CDX-2. All cases of endometrioid carcinomas were negative for both CK20 and CDX-2. All cases of metastatic adenocarcinoma from the colon were negative for CK7 and positive for CK20 and CDX-2. Conclusions: CK7 is an important positive marker for primary ovarian tumors, while CK20 and CDX-2 are useful markers for colorectal carcinoma metastatic to the ovary. Caution should be taken as primary ovarian mucinous tumors may stain positive for CK20, CDX-2, or both, however, they usually exhibit a focal pattern of reactivity.

Keywords: adenoma, endometrioid, malignancy, ovarian

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Authors: Remi Safi, Aline Hamade, Najat Bteich, Jamal El Saghir, Mona Diab Assaf, Marwan El-Sabban, Fadia Najjar

Abstract:

Estrogen is considered a risk factor for breast cancer since it promotes breast-cell proliferation. The jaesckeanadiol-3-p-hydroxyphenylpropanoate, a hemi-synthetic analogue of the natural phytoestrogen ferutinin (jaesckeanadiol-p-hydroxybenzoate), is designed to be devoid of estrogenic activity. This analogue induces a cytotoxic effect 30 times higher than that of ferutinin towards MCF-7 breast cancer cell line. We compared these two compounds with respect to their effect on proliferation, cell cycle distribution and cancer stem-like cells in the MCF-7 cell line. Treatment with ferutinin (30 μM) and its analogue (1 μM) produced a significant accumulation of cells at the pre G0/G1 cell cycle phase and triggered apoptosis. Importantly, this compound retains its anti-proliferative activity against breast cancer stem/progenitor cells that are naturally insensitive to ferutinin at the same dose. These results position ferutinin analogue as an effective compound inhibiting the proliferation of estrogen-dependent breast cancer cells and consistently targeting their stem-like cells.

Keywords: ferutinin, hemi-synthetic analogue, breast cancer, estrogen, stem/progenitor cells

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Authors: Arab M., Ait Abdallah M., Zeraoulia N., Boumaza H., Aoutia M., Griene L., Ait Abdelkader B.,

Abstract:

breast and ovarian cancer are respectively the first and fourth leading causes of cancer among women in Algeria. A family story of cancer in the most important risk factor, and in most cases of families with breast and /or ovarian cancer, the pattern of cancer family can be attributed to mutation in BRCA1/2genes. objectibes: the aim of our study in to investigate the spectrum of BRCA1/2 germiline mutation in familial breast and /or ovarian cancer and to determine the prevalence and the nature of BRCA1/2mutation in Algeria methods: we deremined the prevalence of BRCA1/2 mutation within a cohort of 161 probands selected according the eisinger score double stranded sanger sequencing of all coding exons of BRCA1/2including flanking intronic region were performed results: we identified a total of 23 distinct deleterious mutations (class5) 12 differents mutations in BRCA1(52%) and 11 in BRCA2(48%). 78% (18/23) were protein truncating and 22%(5/23) missens mutations.3 novel deleterious mutations have been identified, which have not been described in public mutation database. one new mutation were found in two unrelated patients. the overall mutation detection rate in our study is 28,5%(46/161).more over, an UVS c7783 located in BRCA2 is found in two unrelated probands and segregate in the 02 families/ conclusion: our results sugget of large spectrum of BRCA1/2 mutation in Algerian breast/ovarian cancer family. The nature and prevalence of BRCA1/2mutation in algerian families are ongoing in a larger study, 80 probands are to day under investigation. This study which may therefore identify the genetic particularity of Algerian breast /ovarian cancer.

Keywords: BRCA1/2 mutations, hereditary breast cancer, algerian women, prvalence

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Authors: V. Yurina, H. Sujuti, E. Rahmani, A. R. Nopitasari

Abstract:

Breast cancer has the highest prevalence cancer in women. Moringa leaves (M. oleifera) contain quercetin, kaempferol, and benzyl isothiocyanate which can enhance induction of apoptosis. This research aimed to study the role of the leaf extract of Moringa to increase apoptosis in breast cancer cell line, MCF-7 cells. This research used in vitro experimental, post-test only, control group design on breast cancer cells MCF-7 in vitro. Moringa leaves were extracted by maceration method with ethanol 70%. Cells were treated with drumstick leaves extract on 1100, 2200, and 4400 μg/ml for Hsp27 and caspase-9 expression (immunocytochemistry) and apoptosis (TUNEL assay) test. The results of this study found that the IC50 2200 µg/ml. Moringa leaves extract can significantly increase the expression of caspase-9 (p<0.05) and decreased Hsp 27 expression (p<0.05). Moreover it can increase apoptosis (p<0.05) significantly in MCF-7 cells. The conclusion of this study is Moringa leaves extract is able to increase the expression of caspase-9, decrease Hsp27 expression and increase apoptosis in breast cancer cell-line MCF-7.

Keywords: apoptosis, breast cancer, caspase-9, Hsp27, Moringa oleifera

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Authors: N. A. Kazemi Sefat, M. M. Mohammadi, J. Hadjati, S. Talebi, M. Ajami, H. Daneshvar

Abstract:

Colorectal cancer metastases result in a significant number of cancer related deaths. Histone deacetylase (HDAC) inhibitors induce growth arrest and apoptosis in a variety of human cancer cells. Sodium butyrate (SB) is a short chain fatty acid, belongs to HDAC inhibitors which is released in the colonic lumen as a consequence of fiber fermentation. In this study, we are about to assess the effect of sodium butyrate on HCT116 human colorectal carcinoma cell line. The viability of cells was measured by microscopic morphologic study and MTT assay. After 48 hours, treatments more than 10 mM lead to cell injury in HCT116 by increasing cell granulation and decreasing cell adhesion (p>0.05). After 72 hours, treatments at 10 mM and more lead to significant cell injury (p<0.05). Our results may suggest that the gene expression which is contributed in cell proliferation and apoptosis has been changed under pressure of HDAC inhibition.

Keywords: colorectal cancer, sodium butyrate, cytotoxicity, MTT

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Authors: K. R. Thabethe, G. A. Adefolaju, M. J. Hosie

Abstract:

Cervical cancer is the third most commonly diagnosed cancer globally and it is one of three AIDS defining malignancies. Highly active antiretroviral therapy (HAART) is a combination of three or more antiretroviral drugs and has been shown to play a significant role in reducing the incidence of some AIDS defining malignancies, although its effect on cervical cancer is still unclear. The aim of this study was to investigate the relationship between cervical cancer and HAART. This was achieved by studying the expression of two signalling molecules expressed in cervical cancer; MUC1 and P65. Following the 24 hour treatment of a cervical cancer cell line, HCS-2, with drugs which are commonly used as part of HAART at their clinical plasma concentrations, real-time qPCR and immunofluorescence were used in order to study gene and protein expression. A one way ANOVA followed by a Tukey Kramer Post Hoc test was conducted using JMP 11 software on both sets of data. The drug classified as a protease inhibitor (PI) (i.e. LPV/r) reduced MUC1 and P65 gene and protein expression more than the other drug tested. PIs are known to play a significant role in cell death, therefore the cells were thought to be more susceptible to cell death following treatment with PIs. In conclusion, the drugs used, especially the PI showed some anticancer effects by facilitating cell death through decreased gene and protein expression of MUC1 and P65 and present promising agents for cancer treatment.

Keywords: cervical cancer, haart, MUC1, P65

Procedia PDF Downloads 297