Medicinal supplement genipin induces p53 and Bax-dependent apoptosis in colon cancer cells

Abstract

Colorectal cancer (CRC) is the third leading cause of cancer-associated mortality worldwide. Genipin is a medicinal herb compound derived from the gardenia fruit, which has been reported to exhibit antitumor activity against several types of cancer. The aim of the present study was to investigate the antitumor effect of genipin on colon cancer and the underlying molecular mechanisms. Genipin significantly inhibited the viability of HCT116 and SW480 cells in vitro in a dose-and time-dependent manner. Additionally, genipin was able to significantly inhibit tumor growth in nude mice with xenografts of HCT116 and SW480 cells. The inhibition of tumor growth by genipin treatment was coupled with G0/G1 cell cycle arrest, apoptosis induction, increased reactive oxygen species damage and loss of mitochondrial membrane potential. Further investigation of genipin-treated HCT116 cells revealed that the expression of p53, Bax and cleaved caspase-3 in genipin-treated cells was increased compared with the vehicle control, whereas B-cell lymphoma-2 expression appeared to be lower in genipin-treated cells. Collectively, the findings of the present study indicate that genipin was able to decrease proliferation and promote apoptosis in colon cancer cells by inducing the p53/Bax-mediated signaling pathway. Therefore, genipin may be used as a novel therapeutic agent in the treatment of CRC.