Sensitization of 5-Fluorouracil-Resistant SNUC5 Colon Cancer Cells to Apoptosis by α-Mangostin.

Abstract

5-fluorouracil (5-FU) is a chemotherapeutic agent commonly used for treatment of solid tumors, including colorectal cancer. However, chemoresistance against 5-fluorouracil (5-FU) often limits its success for chemotherapy and, therefore, finding out appropriate adjuvant(s) that might overcome chemoresistance against 5-FU bears a significant importance. In the present study, we have found that α-mangostin can sensitize 5-FU-resistant SNUC5/5-FUR colon cancer cells to apoptosis. Exposure of α-mangostin induced significant DNA damages and increased the intracellular 8-hydroxyguanosine (8-OH-G) and 4-hydroxynonenal (4-HNE) levels in SNUC5 and SNUC5/5-FUR cells. Western blot analysis illustrated that α-mangostin-induced apoptosis was mediated by the activation of the extrinsic and intrinsic pathways in SNUC5/5-FUR cells. In particular, we observed that Fas receptor (FasR) level was lower in SNUC5/5-FUR cells, compared with SNUC5 cells and that silencing FasR attenuated α-mangostin-mediated apoptosis in SNUC5/5-FUR cells. Together, our study illustrates that α-mangostin might be an efficient apoptosis sensitizer that can overcome chemoresistance against 5-FU by activating apoptosis pathway.