Triptolide-induced apoptosis in p53 mutant hepatoma cells involves ROS-mutant p53- dependent inhibition effect on p21 expression

Chemotherapeutic drugs had poor cytotoxic effects on cancer cells with mutation in the p53 gene. However, triptolide induced apoptosis in tumor cells with mutant (mt) p53. Here we study the potential therapeutic effects and underlying mechanisms of triptolide against human liver cancer cells bearing mt p53. One hepatic cancer cell line with mt p53 (Huh7) and another p53-deficient hepatic cancer cell line (Hep3B) were evaluated for cell proliferation inhibition and apoptosis induction following treatment with triptolide. Triptolide inhibited cell proliferation and induced apoptosis in Huh7 but not Hep3B cells at lower concentrations. In triptolide-treated Huh7 cells, mt p53 and p21 expressions were induced but significant increase of p21 was later than that of mt p53. Increases in the mt p53 and p21 proteins were mediated by enhanced transcriptions resulting from overproduction of ROS. Triptolide rendered Huh7 cells accumulate in S phase. Additionally, triptolide induced p21 and caused cell cycle to be arrested in G1 phase in Hep3B cells. The expression of exogenous mt p53 prevented increase in p21 induced by triptolide and increased apoptosis in Hep3B cells. The above findings suggest that triptolide-induced mt p53, by repressing p21 elevation, accelerates apoptosis in hepatoma cells.