Genipin Induced Apoptosis Associated with Activation of the c-Jun NH2-Terminal Kinase and p53 Protein in HeLa Cells

Abstract

Genipin is a metabolite of geniposide isolated from an extract of Gardenia fructus. Some observations suggested that genipin could induce cell apoptosis in hepatoma cells and PC3 human prostate cancer cells. However, the effects of genipin on HeLa human cervical carcinoma cells are still unknown. In this study, we provided evidences that genipin induced the death of HeLa cells through apoptotic pathway in a dose-dependent manner. Genipin could remarkably induce cytotoxicity in HeLa cells and inhibit its proliferation. Induction of the apoptosis by genipin was confirmed by analysis of DNA fragmentation and induction of sub-G(1) peak through flow cytometry. The results also showed that genipin-treated HeLa cells cycle was arrested at G(1) phase. Western blot analysis revealed that the phosphorylated c-Jun NH(2)-terminal kinase (JNK) protein, phospho-Jun protein, p53 protein and bax protein significantly increased in a dose-dependent manner after treatment of genipin for 24 h, and to our knowledge, the activation of JNK maybe result in the increase of the p53 protein level, and the increase of the p53 protein led to the accumulation of bax protein, bax protein further induced cell apoptotic death eventually. Taken all these together, it is possible to develop genipin as an anti-cancer drug.