Effect and Mechanism of Reactive Oxygen Species on Apoptosis of Human Hepatocellular Carcinoma Cells Induced by Fenretinide
10.3969/j.issn.1008-7125.2014.07.004
- VernacularTitle:活性氧在芬维A胺诱导人肝癌细胞凋亡中的作用及其机制研究
- Author:
Xiaoqin WU
;
Hui YANG
;
Yisheng WEI
;
Aiqun LI
;
Yun ZHONG
;
Hang SU
;
Yuanwei DING
;
Manpeng LIN
- Publication Type:Journal Article
- Keywords:
Carcinoma,Hepatocellular;
Fenretinide;
ReactiveOxygenSpecies;
VitaminE;
Apoptosis
- From:
Chinese Journal of Gastroenterology
2014;(7):399-403
- CountryChina
- Language:Chinese
-
Abstract:
Background:Fenretinide,which is capable of generating reactive oxygen species( ROS ),has emerged as a promising antineoplastic agent based on numerous in vitro and in vivo studies and clinical chemoprevention trials. Preliminary studies showed that fenretinide could induce apoptosis in human hepatocellular carcinoma( HCC)cells in vitro, however,the precise mechanism was not clarified. Aims:To elucidate the effect of ROS on apoptosis of human HCC cells induced by fenretinide and the underlying mechanism. Methods:Human HCC cell line Huh-7 was treated with antioxidant vitamin E,fenretinide or their combination,respectively. ROS in live cells was evaluated by confocal microscopy and flow cytometry;cell viability and apoptosis were assessed by CellTiter-Glo Luminescent Cell Viability Assay Kit and Caspase-Glo3/7 Assay Kit;expression and intracellular localization of nuclear receptor Nur77,as well as expression of stress-induced transcription factor GADD153 were measured by immunofluorescence staining and Western blotting,respectively. Results:Vitamin E pretreatment fully blocked the fenretinide-induced ROS production. In Huh-7 cells pretreated with vitamin E,cell apoptosis induced by fenretinide was significantly reduced(P<0. 05). Furthermore,effect of vitamin E pretreatment was noteworthy on reducing fenretinide-induced GADD153 expression, while no significant impact on fenretinide-induced Nur77 expression and translocation was observed. Conclusions:Elimination of ROS by vitamin E can abrogate the pro-apoptotic effect of fenretinide on Huh-7 cells,which indicates the participation of ROS in fenretinide-induced apoptosis of human HCC cells. Its mechanism might be associated with induction of GADD153 protein expression.
