Melatonin sensitizes Caki renal cancer cells to kahweol-induced apoptosis through CHOP-mediated up-regulation of PUMA
Article first published online: 18 JAN 2011
© 2011 The Authors. Journal of Pineal Research © 2011 John Wiley & Sons A/S
Journal of Pineal Research
Volume 50, Issue 4, pages 359–366, May 2011
How to Cite
Um, H. J., Park, J.-W. and Kwon, T. K. (2011), Melatonin sensitizes Caki renal cancer cells to kahweol-induced apoptosis through CHOP-mediated up-regulation of PUMA. Journal of Pineal Research, 50: 359–366. doi: 10.1111/j.1600-079X.2010.00851.x
- Issue published online: 12 APR 2011
- Article first published online: 18 JAN 2011
- Received November 1, 2010; Accepted December 6, 2010.
- C/EBP homologous protein;
- endoplasmic reticulum stress;
- p53-upregulated modulator of apoptosis
Abstract: Melatonin has recently gained attention as a regulator of biologic processes in addition to its effects on circadian rhythms. The mechanisms whereby melatonin regulates the apoptotic program remain poorly understood. In this study, we investigated the combined effect of melatonin and kahweol on apoptosis of cancer cells, but not in most normal human cell types, thus presenting an attractive novel strategy for cancer treatment. In our experiments, treatment with a combination of melatonin and kahweol induced apoptosis, stimulated DEVDase activity, and DNA fragmentation. Co-treatment with melatonin and kahweol induced up-regulation of p53-upregulated modulator of apoptosis (PUMA) while down-regulation of PUMA expression using small interfering RNAs attenuated melatonin plus kahweol-induced apoptosis. In addition, co-treatment with kahweol and melatonin induced PUMA up-regulation through endoplasmic reticulum stress-mediated C/EBP homologous protein induction and the p53-independent pathway. Our results collectively demonstrate that up-regulation of PUMA contributes to the sensitizing effect of melatonin plus kahweol on apoptosis in cancer cells.