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Evidence-Based Complementary and Alternative Medicine
Volume 2013 (2013), Article ID 629750, 12 pages
http://dx.doi.org/10.1155/2013/629750
Research Article

Involvement of Endoplasmic Reticulum Stress in Capsaicin-Induced Apoptosis of Human Pancreatic Cancer Cells

1Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China
2Department of Hepatobiliary-Pancreatic Surgery, The Second Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang 325027, China

Received 29 September 2012; Revised 31 March 2013; Accepted 23 April 2013

Academic Editor: Taiping Fan

Copyright © 2013 Shengzhang Lin et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Capsaicin, main pungent ingredient of hot chilli peppers, has been shown to have anticarcinogenic effect on various cancer cells through multiple mechanisms. In this study, we investigated the apoptotic effect of capsaicin on human pancreatic cancer cells in both in vitro and in vivo systems, as well as the possible mechanisms involved. In vitro, treatment of both the pancreatic cancer cells (PANC-1 and SW1990) with capsaicin resulted in cells growth inhibition, G0/G1 phase arrest, and apoptosis in a dose-dependent manner. Knockdown of growth arrest- and DNA damage-inducible gene 153 (GADD153), a marker of the endoplasmic-reticulum-stress- (ERS-) mediated apoptosis pathway, by specific siRNA attenuated capsaicin-induced apoptosis both in PANC-1 and SW1990 cells. Moreover, in vivo studies capsaicin effectively inhibited the growth and metabolism of pancreatic cancer and prolonged the survival time of pancreatic cancer xenograft tumor-induced mice. Furthermore, capsaicin increased the expression of some key ERS markers, including glucose-regulated protein 78 (GRP78), phosphoprotein kinase-like endoplasmic reticulum kinase (phosphoPERK), and phosphoeukaryotic initiation factor-2α (phospho-eIF2α), activating transcription factor 4 (ATF4) and GADD153 in tumor tissues. In conclusion, we for the first time provide important evidence to support the involvement of ERS in the induction of apoptosis in pancreatic cancer cells by capsaicin.