Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2015; 21(14): 4169-4177
Published online Apr 14, 2015. doi: 10.3748/wjg.v21.i14.4169
Increase in apoptosis by combination of metformin with silibinin in human colorectal cancer cells
Cheng-Chia Tsai, Tang-Wei Chuang, Li-Jen Chen, Ho-Shan Niu, Kun-Ming Chung, Juei-Tang Cheng, Kao-Chang Lin
Cheng-Chia Tsai, Department of Surgery, Mackay Memorial Hospital, Taipei City 10401, Taiwan
Cheng-Chia Tsai, Graduate Institute of Disease Prevention and Control, College of Medicine, Taipei Medical University, Taipei City 10361, Taiwan
Tang-Wei Chuang, Division of Hepatogastroenterology, Department of Internal Medicine, Chi Mei Medical Center, Liouying 73654, Taiwan
Li-Jen Chen, Institute of Basic Medical Science, College of Medicine, National Cheng Kung University, Tainan City 70101, Taiwan
Ho-Shan Niu, Department of Nursing, Tzu Chi College of Technology, Hualien City 97005, Taiwan
Kun-Ming Chung, Division of Gastroenterology, Department of Internal Medicine, Chi-Mei Medical Center, Yong Kang, Tainan City 71003, Taiwan
Juei-Tang Cheng, Institute of Medical Sciences, Chang Jung Christian University, Gueiren, Tainan City 71101, Taiwan
Kao-Chang Lin, Department of Neurology, Chi Mei Medical Center, Yong Kang, Tainan City 71003, Taiwan
Kao-Chang Lin, Department of Medical Research, Chi Mei Medical Center, Yong Kang, Tainan City 71003, Taiwan
Kao-Chang Lin, Institute of Biotechnology, Southern Taiwan University, Yong Kang, Tainan City 71004, Taiwan
Author contributions: Chuang TW, Tsai CC and Lin KC designed the research; Chen LJ and Niu HS performed the research; Chung KM and Tsai CC analyzed the data; Chen LJ and Cheng JT wrote the paper; Tsai CC and Chuang TW contributed equally to this work.
Supported by A grant from the Chi Mei Medical Center in Taiwan (partly), No. CMFHR10302.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commol/Lons Attribution Non Commol/Lercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commol/Lercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commol/Lercial. See: http://creativecommol/Lons.org/licenses/by-nc/4.0/
Correspondence to: Juei-Tang Cheng, PhD, FCP, Professor, Institute of Medical Sciences, Chang Jung Christian University, Geuiren, Tainan City 71101, Taiwan. jtcheng@mail.cjcu.edu.tw
Telephone: +886-6-331-8516 Fax: +886-6-2386548
Received: July 3, 2014
Peer-review started: July 3, 2014
First decision: July 21, 2014
Revised: October 25, 2014
Accepted: December 22, 2014
Article in press: December 22, 2014
Published online: April 14, 2015
Abstract

AIM: To investigate the effect of metformin on silibinin-induced apoptosis in human colorectal cancer (COLO 205) cells.

METHODS: MTT assays were performed to quantify cell viability. Western blot assays were applied to identify the expression of signaling proteins.

RESULTS: The combined treatment of COLO 205 cells with metformin and silibinin decreased cell survival at a dose insufficient to influence the non-malignant cells [Human colonic epithelial cells (HCoEpiC)]. Silibinin and metformin increased phosphatase and tensin homolog and 5’-adenosine monophosphate-activated protein kinase expression in COLO 205 cells and inhibited the phosphorylation of mammol/Lalian target of rapamycin. This combined treatment resulted in an increase in the expression of activated caspase 3 and apoptosis inducing factor, indicating apoptosis.

CONCLUSION: The combined treatment of human colorectal cancer cells with silibinin and metformin may induce apoptosis at a dose that does not affect HCoEpiC. This finding reveals a potential therapeutic strategy for the treatment of colorectal cancer.

Keywords: Silibinin, Metformin, COLO 205, Mammol/Lalian target of rapamycin, Apoptosis, Colorectal cancer

Core tip: Silibinin is known to provide protection against hepatotoxic stress. Silibinin has also been shown to have high efficacy against cancer cells through increased expression of the phosphatase and tensin homolog; Metformin, a well-known antidiabetic agent, has recently been reported to inhibit cancer by increasing adenosine monophosphate-activated protein kinase expression. We investigated the effect of metformin on silibinin-induced apoptosis in human colorectal cancer cells. The combined treatment of human colorectal cancer cells with silibinin and metformin may induce apoptosis at a dose that does not affect human colonic epithelial cells. This finding reveals a potential therapeutic strategy for the treatment of colorectal cancer.