Original Article
Copyright ©2014 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jan 7, 2014; 20(1): 193-203
Published online Jan 7, 2014. doi: 10.3748/wjg.v20.i1.193
Apoptotic pathway induced by diallyl trisulfide in pancreatic cancer cells
Hong-Bing Ma, Shan Huang, Xiao-Ran Yin, Yang Zhang, Zheng-Li Di
Hong-Bing Ma, Shan Huang, Xiao-Ran Yin, Yang Zhang, Department of Radiotherapy of Tumor Hospital, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
Zheng-Li Di, Department of Neurology, Xi’an Center Hospital, Xi’an 710004, Shaanxi Province, China
Author contributions: Ma HB and Di ZL performed the majority of experiments; Yin XR and Zhang Y provided vital reagents and analytical tools and revised the manuscript; Ma HB and Huang S designed the study and wrote the manuscript.
Supported by Fund for Science and Technology Program of Shaanxi Province, China, No. 2010K01-141
Correspondence to: Hong-Bing Ma, PhD, Department of Radiotherapy of Tumor Hospital, the Second Hospital of Xian Jiaotong University, No. 157, Xiwulu, Xi’an 710004, Shaanxi Province, China. mhbxian@126.com
Telephone: +86-29-87679789 Fax: +86-29-87679789
Received: June 7, 2013
Revised: October 17, 2013
Accepted: November 2, 2013
Published online: January 7, 2014
Abstract

AIM: To investigate the effects of diallyl trisulfide (DATS), a garlic-derived organosulfur compound, in pancreatic cancer cells.

METHODS: Human pancreatic cancer cells with wild-type p53 gene (Capan-2) and normal pancreatic epithelial cells (H6C7) were cultured in RPMI1640. DATS was prepared at a concentration of 100 μmol/L. Cell viability was determined via the methyl thiazolyl tetrazolium assay. Apoptotic cells were detected by TUNEL assay. Cell cycle analysis was performed using flow cytometry. Protein expression was determined by Western blot. Bax and Bcl-2 expression was detected by immunofluorescence. Apoptosis genes and cell cycle were assessed by quantitative real-time polymerase chain reaction.

RESULTS: DATS suppressed the viability of cultured human pancreatic cancer cells (Capan-2) by increasing the proportion of cells in the G2/M phase and induced apoptotic cell death. Western blot analysis indicated that DATS enhanced the expression of Fas, p21, p53 and cyclin B1, but downregulated the expression of Akt, cyclin D1, MDM2 and Bcl-2. DATS induced cell cycle inhibition which was correlated with elevated levels of cyclin B1 and p21, and reduced levels of cyclin D1 in Capan-2 cells and H6C7 cells. DATS-induced apoptosis was markedly elevated in Capan-2 cells compared with H6C7 cells, and this was correlated with elevated levels of cyclin B1 and p53, and reduced levels of Bcl-2. DATS-induced apoptosis was correlated with down-regulation of Bcl-2, Akt and cyclin D1 protein levels, and up-regulation of Bax, Fas, p53 and cyclin B protein levels in Capan-2 cells.

CONCLUSION: DATS induces apoptosis of pancreatic cancer cells (Capan-2) and non-tumorigenic pancreatic ductal epithelial cells (H6C7).

Keywords: Diallyl trisulfide, Apoptosis, Pancreatic cancer, Cell cycle, p53

Core tip: We investigated the effect of diallyl trisulfide (DATS), a promising cancer chemopreventive constituent of processed garlic, in human pancreatic cancer cells (Capan-2) and non-tumorigenic pancreatic ductal epithelial cells (H6C7), and explored the possible mechanism involved. We found that DATS can induce apoptosis in both cell lines. We also investigated the role of p53, Bcl-2 and the cell cycle in apoptosis of Capan-2 and H6C7 cells.