title: 6-Gingerol Mediates its Anti Tumor Activities in Human Oral and Cervical Cancer Cell Lines through Apoptosis and Cell Cycle Arrest.
abstract: 6-Gingerol, a potent nutraceutical, has been shown to have antitumor activity in different tumors, although its mechanism of action is not well understood. In this study, we evaluated antitumor activities of 6-gingerol on human oral (SCC4, KB) and cervical cancer (HeLa) cell lines with or without wortmannin, rapamycin, and cisplatin. Tumor cell proliferation was observed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium, inner salt assay, cell cycle analysis by propidium iodide labeling and flow cytometry, apoptosis by Annexin-V binding assay, and caspase activity by chemiluminescence assay. 6-Gingerol showed dose-dependent cytotoxicity in all three cell lines. Combinations of 6-gingerol with wortmannin and cisplatin showed additive effects, while with rapamycin, it showed 50% cytotoxicity that was equivalent to IC50 of 6-gingerol alone. Treatment with 6-gingerol resulted in G2-phase arrest in KB and HeLa cells and S-phase arrest in SCC4 cells. 6-Gingerol, wortmannin, and rapamycin treatment showed almost two-fold higher expression of caspase 3 in all cell lines. The results imply that 6-gingerol either alone or in combination with PI-3 K inhibitor and cisplatin may provide better therapeutic effects in oral and cervical carcinoma. Thus, 6-gingerol appears to be a safe and potent chemotherapeutic/chemopreventive compound acting through cell cycle arrest and induction of apoptosis in human oral and cervical tumor cells.
authors.affiliation: Department of Biotechnology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.
authors.forename: Vaishali
authors.initials: V
authors.lastname: Kapoor
authors.affiliation: Department of Biotechnology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.
authors.forename: Sadhna
authors.initials: S
authors.lastname: Aggarwal
authors.affiliation: Department of Biotechnology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.
authors.forename: Satya N
authors.identifier: http://orcid.org/0000-0002-1659-2499
authors.initials: SN
authors.lastname: Das
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002396:Catechols / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D005233:Fatty Alcohols / Q000494:pharmacology*; D005260:Female; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D009062:Mouth Neoplasms / Q000473:pathology*; D020123:Sirolimus / Q000494:pharmacology; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000473:pathology*; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D002396:Catechols; D005233:Fatty Alcohols; C007845:gingerol; C505407:CASP3 protein, human; D053148:Caspase 3; D002945:Cisplatin; D020123:Sirolimus; D000077191:Wortmannin
keywords: 6-gingerol; apoptosis; cell cycle; cervical cancer; oral cancer