JIB-04 induces cell apoptosis via activation of the p53/Bcl-2/caspase pathway in MHCC97H and HepG2 cells

Abstract

JIB-04 is a structurally unique small molecule, known to exhibit anticancer activity and to inhibit the growth of human lung cancer and prostate cancer cell lines. However, the anticancer effect of JIB-04 against human hepatic carcinoma, and its underlying mechanisms, are still unclear. In the present study, MHCC97H and HepG2 cells were employed to investigate the anticancer effects of JIB-04 on cell viability and apoptosis. Annexin V/PI staining, a CCK-8 assay and western blot analysis demonstrated that JIB-04 induced apoptosis in MHCC97H and HepG2 cells, which was evidenced by the expression of proapoptotic and apoptotic proteins including p53, Bak, Bax, caspase-3 and caspase-9. Subsequently, the expression trends of Bcl-2 and p53 were reversed after co-treatment with pifithrin-α (PFT-α, a p53 inhibitor). The results revealed that JIB-04 suppressed the cell viability of MHCC97H and HepG2 cells in a concentration-dependent manner. Meanwhile, it was also demonstrated that JIB-04 effectively triggered MHCC97H and HepG2 cell apoptosis by downregulating Bcl-2/Bax expression, and upregulating proapoptotic and apoptotic protein expression via the p53/Bcl2/caspase signaling pathway. JIB-04 had effects on the inhibition of cell viability and the induction of apoptosis in MHCC97H and HepG2 cells. The underlying mechanism of action of JIB-04 was associated with the p53/Bcl-2/caspase signaling pathway. Our findings provide a foundation for understanding the anticancer effect of JIB-04 on MHCC97H and HepG2 cells, and suggested that JIB-04 may be a promising therapeutic agent in human liver cancer.