Melatonin sensitizes Caki renal cancer cells to kahweol-induced apoptosis through CHOP-mediated up-regulation of PUMA

Authors
Hee Jung UmJong-Wook ParkTaeg Kyu Kwon
Department
Dept. of Immunology (면역학)
Issue Date
2011
Citation
Journal of Pineal Research, Vol.50(4) : 359-366, 2011
ISSN
0742-3098
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.
Keywords
apoptosisC/EBP homologous proteinendoplasmic reticulum stresskahweolmelatoninp53-upregulated modulator of apoptosis
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/33879
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
Keimyung Author(s)
박종욱; 권택규
Full Text
http://lps3.onlinelibrary.wiley.com.proxy.dsmc.or.kr/doi/abs/10.1111/j.1600-079X.2010.00851.x
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