Guggulsterone induces apoptosis in colon cancer cells and inhibits tumor growth in murine colorectal cancer xenografts

Abstract

[한글]

[영문]The plant sterol guggulsterone has recently been shown to have anti-inflammatory properties and anti-tumorigenic potential in certain cancer cell types. In this study, I investigated the anti-tumorigenic effects of guggulsterone and elucidated its molecular mechanisms in HT-29 human colon cancer cells and murine xenografts. In the present study, I determined whether guggulsterone induces apoptosis in HT-29 colon cancer cells in vitro, and the mechanism by which it does so. Furthermore, we carried out in vivo studies to examine the effect of guggulsterone in a colon cancer HT-29 xenograft model. Guggulsterone significantly suppressed cell viability and increased apoptosis in HT-29 cells in a dose-dependent manner by activating caspase-3 and caspase-8. Furthermore, guggulsterone decreased cIAP-1, cIAP-2, and Bcl-2 levels and increased the levels of truncated Bid, Fas, p-JNK, and p-c-Jun. The size of HT-29 xenograft tumors in guggulsterone-treated mice was significantly smaller than of the size of tumors in control mice. Immunohistochemical staining showed that Bcl-2 expression in tumor xenografts was inhibited by guggulsterone treatment. The present study indicates that guggulsterone induces apoptosis in HT-29 human colon cancer cells and inhibits the growth of HT-29 xenograft tumors in vivo, suggesting a potential therapeutic use for this compound in the treatment of colorectal cancer.