Overexpression of CYP2E1 enhances sensitivity of HepG2 cells to Fas-mediated cytotoxicity

• Published in: Cancer biology & therapy 2008-08, Vol.7 (8), p.1280-1287
• Main Authors: Yan, Qing-Guo, Shi, Jian-Guo, Zhang, Feng, Zhao, Qing-Tao, Pang, Xiao-Wen, Chen, Rui, Hu, Pei-Zhen, Li, Qin-Long, Wang, Zhe, Huang, Gao-Sheng
• Format: Article
• Language: English
• Subjects: Adenoviridae - genetics; Adenoviridae - metabolism; Apoptosis - drug effects; Apoptosis - genetics; Binding; Biology; Bioscience; Calcium; Cancer; Carcinoma, Hepatocellular - pathology; Cell; Cycle; Cytochrome P-450 CYP2E1 - biosynthesis; Cytochrome P-450 CYP2E1 - genetics; Cytochrome P-450 CYP2E1 - metabolism; Fas Ligand Protein - genetics; Fas Ligand Protein - pharmacology; fas Receptor - genetics; fas Receptor - metabolism; Humans; Landes; Liver Neoplasms - pathology; Organogenesis; Oxidative Stress - drug effects; Oxidative Stress - genetics; Proteins
• ISSN: 1538-4047; 1555-8576
• DOI: 10.4161/cbt.7.8.6283

Hepatocellular carcinoma (HCC) has been reported to be resistant to Fas-mediated apoptosis. In present study, experiments were conducted to investigate the potential effects of CYP2E1 overexpression on susceptibility of HCC to Fas-mediated cytotoxicity. HCC cell line HepG2 was infected with Ad-CYP2E1 to enhance the expression of CYP2E1, followed by treatment with low toxic dose of recombinant human Fas ligand (FasL, 0.5ng/ml) in the presence of Actinomycin D (Act D, 125ng/ml). High level of Fas expression was found in HepG2 cells. Its protein level and distribution kept unchanged after different treatments. Compared with control, CYP2E1 expressed HepG2 cells were more sensitive to FasL plus Act D. The sensitivity was elevated in a multiplicity of infection (m.o.i)-dependent manner, which was dramatically suppressed by CYP2E1 inhibitor diallyl disulfide (DAS) (P