期刊
FEBS OPEN BIO
卷 4, 期 -, 页码 763-776出版社
WILEY
DOI: 10.1016/j.fob.2014.08.005
关键词
Curcumin; Glioma; Autophagy; ROS; Par-4; Ceramide
资金
- UAEU-NRF [31M097]
- Sheikh Hamdan Award for Medical Sciences [MGR-60/2011-2012]
- Terry Fox Foundation for Cancer Research [SGC-pmr-7091-2004]
- College of Medicine and Health Sciences, UAE University grant
- Al Jalila Foundation for Medical Education and Research
Malignant gliomas are extremely resistant to therapies that induce apoptosis, but are less resistant to therapies that induce autophagy. Therefore, drugs targeting autophagy are promising in the management of malignant gliomas. In this study, we investigated the anti-glioma potential of curcumin in vitro, and further examined the molecular mechanisms of curcumin-induced cell death in human malignant glioma. Here, we provide evidence that curcumin is cytotoxic against human malignant glioma cell lines, and the mechanism of cell death caused by curcumin is associated with features of autophagy. Curcumin suppresses the growth of human malignant glioma cells via ROS-dependent prostate apoptosis response-4 (Par-4) induction and ceramide generation. Extracellular supplementation of antioxidants such as glutathione and N-acetylcysteine to glioma cells abrogated the Par-4 induction, ceramide generation, and in turn, prevented curcumin-induced autophagic cell death. Moreover, tumor cells transfected with Par-4 gene sensitized the curcumin-induced autophagic cell death. Overall, this study describes a novel signaling pathway by which curcumin induces ROS-dependent Par-4 activation and ceramide generation, leading to autophagic cell death in human malignant glioma cells. (C) 2014 The Authors. Published by Elsevier B. V. on behalf of the Federation of European Biochemical Societies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据