Commenced in January 2007
Paper Count: 30835
Ellagic Acid Enhanced Apoptotic Radiosensitivity via G1 Cell Cycle Arrest and γ-H2AX Foci Formation in HeLa Cells in vitro
Abstract:Radiation therapy is an effective vital strategy used globally in the treatment of cervical cancer. However, radiation efficacy principally depends on the radiosensitivity of the tumor, and not all patient exhibit significant response to irradiation. A radiosensitive tumor is easier to cure than a radioresistant tumor which later advances to local recurrence and metastasis. Herbal polyphenols are gaining attention for exhibiting radiosensitization through various signaling. Current work focuses to study the radiosensitization effect of ellagic acid (EA), on HeLa cells. EA intermediated radiosensitization of HeLa cells was due to the induction γ-H2AX foci formation, G1 phase cell cycle arrest, and loss of reproductive potential, growth inhibition, drop in the mitochondrial membrane potential and protein expression studies that eventually induced apoptosis. Irradiation of HeLa in presence of EA (10 μM) to doses of 2 and 4 Gy γ-radiation produced marked tumor cytotoxicity. EA also demonstrated radio-protective effect on normal cell, NIH3T3 and aided recovery from the radiation damage. Our results advocate EA to be an effective adjuvant for improving cancer radiotherapy as it displays striking tumor cytotoxicity and reduced normal cell damage instigated by irradiation.
Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1131926Procedia APA BibTeX Chicago EndNote Harvard JSON MLA RIS XML ISO 690 PDF Downloads 487
 Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM: “Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008”. Int J Cancer 2008, 2010 (127):2893-2917.
 Oltval ZN, Milliman CL, Korsmeyer SJ. “ Bcl-2 heterodimerizes in vivo with a conserved homolog, bax, that accelerates programmed cell death”. Cell 1993, 74:609-619.
 Earnshaw WC, Martins LM, Kaufmann SH. “Mammalian caspases: Structure, activation, substrates, and functions during apoptosis”. Annual Review of Biochemistry 1999, 68:383-424.
 Shah S, Gapor A, Sylvester PW. “ Role of caspase-8 activation in mediating vitamin E-induced apoptosis in murine mammary cancer cells”. Nutrition and Cancer 2003, 45:236-246.
 Huang EY, Wang CJ, Chen HC, Fang FM, Huang YJ, Wang CY, Hsu HC. “Multivariate analysis of para-aortic lymph node recurrence after definitive radiotherapy for stage IB-IVA squamous cell carcinoma of uterine cervix”.Int J Radiat Oncol Biol Phys 2008, 72:834-842.
 Hockel M, Schlenger K, Aral B, Mitze M, Schaffer U, Vaupel P. “Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix”. Cancer Res 1996, 56:4509-4515
 Rofstad EK, Sundfør K, Lyng H, Tropé CG. “Hypoxia-induced treatment failure in advanced squamous cell carcinoma of the uterine cervix is primarily due to hypoxia-induced radiation resistance rather than hypoxia-induced metastasis”. Br J Cancer 2000, 83:354-359.
 Parliament MB, Murray D. “Single nucleotide polymorphisms of DNA repair genes as predictors of radioresponse”. Semin Radiat Oncol 2010, 20:232-240.
 Hertlein L, Lenhard M, Kirschenhofer A, Kahlert S, Mayr D, Burges A, Friese K. “Cetuximab monotherapy in advanced cervical cancer: a retrospectivestudy with five patients”. Arch Gynecol Obstet 2011, 283:109-113.
 Kurtz JE, Hardy-Bessard AC, Deslandres M, Lavau-Denes S, Largillier R, Roemer-Becuwe C, Weber B, Guillemet C, Paraiso D, Pujade-Lauraine E. “Cetuximab, topotecan and cisplatin for the treatment of advanced cervical cancer: a phase II GINECO trial”. Gynecol Oncol 2009,113:16-20.
 Gaffney DK, Winter K, Dicker AP, Miller B, Eifel PJ, Ryu J, Avizonis V, Fromm M, Small W, Greven K. “Efficacy and patterns of failure for locally advanced cancer of the cervix treated with celebrex (celecoxib) and chemoradiotherapy in RTOG 0128”. Int J Radiat Oncol Biol Phys 2007, 69:111-117.
 Herrera FG, Chan P, Doll C, Milosevic M, Oza A, Syed A, Pintilie M, Levin W, Manchul L, Fyles A. “A prospective phase I-II trial of the cyclooxygenase-2 inhibitor celecoxib in patients with carcinoma of the cervix with biomarker assessment of the tumor microenvironment”. Int J Radiat Oncol Biol Phys 2007, 67:97-103
 Kim TJ, Lee JW, Song SY, Choi JJ, Choi CH, Kim BG, Lee JH, Bae DS. “Increased expression of pAKT is associated with radiation resistance in cervical cancer”.Br J Cancer 2006, 94:1678-1682.
 Lee CM, Shrieve DC, Zempolich KA, Lee RJ, Hammond E, Handrahan DL, Gaffney DK. “Correlation between human epidermal growth factor receptor family (EGFR, HER2, HER3, HER4), phosphorylated Akt (P-Akt), and clinical outcomes after radiation therapy in carcinoma of the cervix”. Gynecol Oncol 2005, 99:415-421.
 Bharat B Aggarwal, Haruyo Ichikawa, Prachi Garodia, Priya Weerasinghe,Gautam Sethi, Indra D Bhatt et.al. “From traditional Ayurvedic medicine to modern medicine:identification of therapeutic targets for suppression of inflammation and cancer”. Expert Opin. Ther. Targets (2006) 10(1)
 VR Ahire, KP Mishra, G. K. (2015). “Apoptotic Radiosensitivity of Cervical Tumor Cells Enhanced by Ellagic Acid”. EJBB.2015. 3(4) 56-58
 S.Girdhani , SM Bhosle, SA Thulsidas, AKumar, KP Mishra . “Potential of radiosensitizing agents in cancer chemo-radiotherapy”. Journal of Cancer Research and Therapeutics, 2005.1(3), 129.
 VR Ahire, KP Mishra, GR Kulkarni. “On the mechanism of cellular toxicity in breast cancer by ionizing radiation and chemotherapeutic drugs”. JEPTO, 2014.33(1), 69–82.
 SM Bhosle, VR Ahire, MS Henry, VS Thakur, NG Huilgol, KP Mishra. “Augmentation of radiation-induced apoptosis by ellagic acid”. Cancer Investigation, 2010. 28(3), 323–30.
 B Kumar, A Kumar, BN Pandey, BHazra, KP Mishra. “Increased cytotoxicity by the combination of radiation and diospyrin diethylether in fibrosarcoma in culture and in tumor”. International Journal of Radiation Biology, 2008. 84(5), 429-40.