title: 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.
authors.affiliation: College of Pharmacy, Dongguk University, Goyang 10326, Republic of Korea.
authors.forename: June
authors.initials: J
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Dongguk University, Goyang 10326, Republic of Korea.
authors.forename: Jong-Su
authors.initials: JS
authors.lastname: Kang
authors.affiliation: Department of Pharmaceutical Science and Engineering, Seowon University, Cheongju 28674, Republic of Korea.
authors.forename: Bu-Young
authors.initials: BY
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Dongguk University, Goyang 10326, Republic of Korea.
authors.forename: Young-Sam
authors.initials: YS
authors.lastname: Keum
keywords: 5-fluorouracil (5-FU); Apoptosis; Oxidative damages; α-mangostin