Sensitization of 5-Fluorouracil-Resistant SNUC5 Colon Cancer Cells to Apoptosis by α-Mangostin.
10.4062/biomolther.2016.028
- Author:
June LEE
1
;
Jong Su KANG
;
Bu Young CHOI
;
Young Sam KEUM
Author Information
1. College of Pharmacy, Dongguk University, Goyang 10326, Republic of Korea. keum03@dongguk.edu
- Publication Type:Original Article
- Keywords:
5-fluorouracil (5-FU);
α-mangostin;
Oxidative damages;
Apoptosis
- MeSH:
Antigens, CD95;
Apoptosis*;
Blotting, Western;
Colon*;
Colonic Neoplasms*;
Colorectal Neoplasms;
DNA Damage;
Drug Therapy;
Fluorouracil
- From:Biomolecules & Therapeutics
2016;24(6):604-609
- CountryRepublic of Korea
- Language:English
-
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.
