title: Withaferin A induces apoptosis through the generation of thiol oxidation in human head and neck cancer cells.
abstract: Withaferin A is a steroidal lactone purified from the Indian medicinal plant, Withania somnifera. Withaferin A has been shown to inhibit the proliferation, metastasis, invasion and angiogenesis of cancer cells. In the present study, we investigated whether withaferin A induces apoptosis in the human head and neck cancer cells, AMC-HN4. Withaferin A markedly increased the sub-G1 cell population and the cleavage of poly(ADP-ribose) polymerase (PARP), which are markers of apoptosis. Pan-caspase inhibitor, z-VAD-fmk (z-VAD), markedly inhibited the withaferin A-induced apoptosis. However, the withaferin A-induced increase in the expression of COX-2 was not affected by treatment with z-VAD. Furthermore, withaferin A upregulated cyclooxygenase-2 (COX-2) expression. The COX-2 inhibitor, NS-398, reduced the withaferin A-induced production of prostaglandin E2. However, treatment with NS-398 did not affect the sub-G1 population and the cleavage of PARP. In addition, the withaferin A-induced apoptosis was independent of reactive oxygen species production. Thiol donors [N-acetylcysteine (NAC) and dithiothreitol (DTT)] reversed withaferin A-induced apoptosis. Therefore, our data suggest that withaferin A induces apoptosis through the mechanism of thiol oxidation in head and neck carcinoma cells.
authors.affiliation: Department of Otolaryngology, School of Medicine, Keimyung University, Dalseo-Gu, Daegu 704-701, Republic of Korea.
authors.forename: Jong Won
authors.initials: JW
authors.lastname: Park
authors.affiliation: Department of Immunology, School of Medicine, Keimyung University, Dalseo-Gu, Daegu 704-701, Republic of Korea.
authors.forename: Kyoung-Jin
authors.initials: KJ
authors.lastname: Min
authors.affiliation: Department of Otolaryngology, School of Medicine, Keimyung University, Dalseo-Gu, Daegu 704-701, Republic of Korea.
authors.forename: Dong Eun
authors.initials: DE
authors.lastname: Kim
authors.affiliation: Department of Immunology, School of Medicine, Keimyung University, Dalseo-Gu, Daegu 704-701, Republic of Korea.
authors.forename: Taeg Kyu
authors.initials: TK
authors.lastname: Kwon
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D054358:Withanolides / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D054358:Withanolides; D051546:Cyclooxygenase 2; C009684:withaferin A