Genipin as the Active Compound of Gardenia fruits Inhibit Proliferation, Migration and Autophagy of Prostate Cancer through PI3K/AKT Signaling Pathway

Abstract

Purpose:Prostate cancer is the second most diagnosed cancer type and the most common cause of cancer-related deaths in men. Genipin is a protein cross-linking agent extracted from Gardenia (Gardenia jasminoides Ellis) fruits, 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 prostate cancer and the underlying molecular mechanisms.Methods:CCK-8 assays were performed to determine the cell viability of genipin prostate cancer cells lines (DU145, PC-3, RM-1) and normal prostate cell lines (WPMY1). Colony formation assays, and wound-healing assays used to detect the effect of genipin on DU145, PC-3 and RM-1 cell lines. Immunofluorescence and western blotting were carried out to investigate its mechanism.Results:Genipin inhibited the survival of DU-145, PC-3 and RM-1 cells in a time-dependent and dose-dependent manner. And Genipin induced apoptosis of prostate carcinoma cells, including DU-145, PC-3 and RM-1 cells. Moreover, the expression of p62 in DU-145 and PC-3 cells was down-regulated, whereas Beclin1 and LC3II/ I were up-regulated. In addition, genipin also decreased p-PI3K, p-AKT, p-NF-\(\kappa\)B and p-mTOR.Conclusion:Genipin is the active compound to inhibit proliferation and migration of prostate cancer through PI3K/AKT/NF-\(\kappa\)B signaling pathway and promoted prostate cancer cells autophagy through PI3K/AKT/mTOR signaling pathway, indicating that Genipin may serve as a potential lead drug for prostate cancer treatment. Therefore, Genipin may be used as a novel therapeutic agent in the treatment of prostate cancer.