Cytochrome P450 2E1 increases the sensitivity of hepatoma cells to vitamin K2.
Although vitamin K2 (VK2) exhibits inhibitory effects on the viability of hepatoma cells, hepatoma cells are insensitive to VK2. Therefore, this investigation is an attempt to enhance the sensitivity of hepatoma cells to VK2. Our results showed that VK2 acted synergistically with ethanol (EtOH) to inhibit the viability of Smmc-7721 cells, mainly because cytochrome P450 2E1 (CYP2E1) was activated by EtOH. The synergistic effect of VK2 and EtOH was also observed in QGY-7703 cells, which also express CYP2E1. However, in HepG2 cells, which do not express CYP2E1, the synergistic effect of VK2 and EtOH was not observed. In addition, we demonstrated that CYP2E1 could be induced by VK2 via both post-transcriptional and transcriptional mechanisms. These results suggest that induction of CYP2E1 can enhance the inhibitory effect of VK2 on the viability of hepatoma cells. CYP2E1 may be an attractive target for enhanced antitumor effects of VK2 in hepatocellular carcinoma treatment.
Department of Biochemistry and Molecular Biology, Anhui University of Chinese Medicine, Hefei, Anhui 230012, P.R. China.
Lu
L
Li
Department of Pharmacology, Anhui University of Chinese Medicine, Hefei, Anhui 230012, P.R. China.
Lu
L
Wang
Department of Biochemistry and Molecular Biology, Anhui University of Chinese Medicine, Hefei, Anhui 230012, P.R. China.
Rui
R
Song
Institute of Combined Traditional Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, Anhui 230012, P.R. China.
Guangliang
G
Chen
Department of Biochemistry and Molecular Biology, Anhui University of Chinese Medicine, Hefei, Anhui 230012, P.R. China.
Yanyan
Y
Liu
D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis / Q000235:genetics*; D004357:Drug Synergism; D000431:Ethanol / Q000008:administration & dosage*; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D024482:Vitamin K 2 / Q000008:administration & dosage*
D024482:Vitamin K 2; D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1