Withaferin A induces apoptosis through the generation of thiol oxidation in human head and neck cancer cells

Park,Jong  Won; Min,Kyoung-Jin; Kim,Dong  Eun; Kwon,Taeg  Kyu

doi:10.3892/ijmm.2014.1983

Withaferin A induces apoptosis through the generation of thiol oxidation in human head and neck cancer cells

Authors:
- Jong Won Park
- Kyoung-Jin Min
- Dong Eun Kim
- Taeg Kyu Kwon
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Affiliations: Department of Otolaryngology, School of Medicine, Keimyung University, Dalseo-Gu, Daegu 704-701, Republic of Korea, Department of Immunology, School of Medicine, Keimyung University, Dalseo-Gu, Daegu 704-701, Republic of Korea
Published online on: October 27, 2014 https://doi.org/10.3892/ijmm.2014.1983
Pages: 247-252

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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.

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