title: Naringin induces death receptor and mitochondria-mediated apoptosis in human cervical cancer (SiHa) cells.
abstract: Cervical cancer is the second most common female cancer worldwide, and it remains a challenge to manage preinvasive and invasive lesions. Fruit-based cancer prevention entities, such as flavonoid and their derivatives, have demonstrated a marked ability to inhibit preclinical models of epithelial cancer cell growth and tumor formation. Here, we extend the role of naringin-mediated chemoprevention to that of cervical carcinogenesis. The present study sought to investigate the therapeutic potential effect of naringin on apoptosis in human cervical SiHa cancer cells. Viability of SiHa cells was evaluated by the MTT assay, apoptosis and mitochondrial transmembrane potential by flow cytometry, and pro-apoptotic related genes by Real-time quantitative PCR. Naringin showed a 50% inhibition of SiHa human cervical cancer cells at a concentration of 750μM. SiHa cells exhibited apoptotic cell death, intranucleosomal DNA fragmentation, morphological changes and decline in the mitochondrial transmembrane potential. In addition, administration of naringin increased the expression of caspases, p53 and Bax, Fas death receptor and its adaptor protein FADD. These results suggest that the induction of apoptosis by naringin is through both death-receptor and mitochondrial pathways. Taken together, our results suggest that naringin might be an effective agent to treat human cervical cancer.
authors: Department of Food Science and Nutrition, King Saud University, Riyadh 11451, Saudi Arabia.
authors: E
authors: E
authors: Ramesh
authors: Ali A
authors: AA
authors: Alshatwi
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D053200:Fas-Associated Death Domain Protein / Q000235:genetics / Q000378:metabolism; D005260:Female; D044950:Flavanones / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016158:Genes, p53; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; C505533:FADD protein, human; C491901:FAS protein, human; D053200:Fas-Associated Death Domain Protein; D044950:Flavanones; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D020169:Caspases; C005274:naringin