Biomol Ther.  2016 Nov;24(6):604-609. 10.4062/biomolther.2016.028.

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

• Lee J
• Kang JS
• Choi BY
• Keum YS

• KMID: 2374614
• DOI: http://doi.org/10.4062/biomolther.2016.028

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.

Keyword

5-fluorouracil (5-FU); α-mangostin; Oxidative damages; Apoptosis

MeSH Terms

Antigens, CD95
Apoptosis*
Blotting, Western
Colon*
Colonic Neoplasms*
Colorectal Neoplasms
DNA Damage
Drug Therapy
Fluorouracil
Antigens, CD95
Fluorouracil