Phenethyl isothiocyanate sensitizes human cervical cancer cells to apoptosis induced by cisplatin
Version of Record online: 19 MAY 2011
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 55, Issue 10, pages 1572–1581, October 2011
How to Cite
Wang, X., Govind, S., Sajankila, S. P., Mi, L., Roy, R. and Chung, F.-L. (2011), Phenethyl isothiocyanate sensitizes human cervical cancer cells to apoptosis induced by cisplatin. Mol. Nutr. Food Res., 55: 1572–1581. doi: 10.1002/mnfr.201000560
- Issue online: 10 OCT 2011
- Version of Record online: 19 MAY 2011
- Manuscript Accepted: 10 MAR 2011
- Manuscript Revised: 11 FEB 2011
- Manuscript Received: 11 NOV 2010
- NCI. Grant Number: CA 100853
- ERK activation;
- Phenethyl isothiocyanate;
Scope: Naturally-occurring chemopreventive agent phenethyl isothiocyanate (PEITC), derived primarily from watercress, has been shown to inhibit cell growth and induce apoptosis in cancer cells. In this study, we examined the potential of PEITC in enhancing cisplatin-induced apoptosis in cervical cancer cells and its mechanisms.
Methods and results: HeLa cells were exposed to PEITC, cisplatin or both. Pretreatment of cells with PEITC strongly enhanced cisplatin-induced cytotoxicity. PEITC activated the mitogen-activated protein kinases, including c-Jun N-terminal kinase (JNK), extracellular signal-related kinase (ERK), and p38. Caspase-3 activity assay demonstrated that the synergistic induction of apoptosis was significantly attenuated by MEK1/2 inhibitor U0126, but not by JNK or p38 inhibitor, suggesting that ERK activation is responsible for the synergistic effect. We found that NF-κB signaling pathway is not involved in the synergistic effect. Sulforaphane and benzyl isothiocyanate, two other members of the isothiocyanate family, also sensitize HeLa cells to apoptosis induced by cisplatin. Furthermore, we found that the synergistic effect was also observed in cervical cancer C33A and breast cancer MCF-7 cells but not in normal mammary epithelial MCF-10A cells. Finally, we demonstrated that Noxa induction was associated with apoptosis induced by PEITC plus cisplatin.
Conclusion: Taken together, this study shows that PEITC can sensitize cancer cells to apoptosis induced by cisplatin and this effect is mediated through ERK activation, suggesting the potential of PEITC to be used as an adjuvant with cisplatin in combination therapeutic treatments.