title: Involvement of endoplasmic reticulum stress in capsaicin-induced apoptosis of human pancreatic cancer cells.
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-2 α (phospho-eIF2 α ), 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.
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China ; Department of Hepatobiliary-Pancreatic Surgery, The Second Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang 325027, China.
authors.forename: Shengzhang
authors.initials: S
authors.lastname: Lin
authors.forename: Jianhong
authors.initials: J
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Kangjie
authors.initials: K
authors.lastname: Chen
authors.forename: Fuji
authors.initials: F
authors.lastname: Lai
authors.forename: Jiang
authors.initials: J
authors.lastname: Luo
authors.forename: Zhaohong
authors.initials: Z
authors.lastname: Wang
authors.forename: Heqi
authors.initials: H
authors.lastname: Bu
authors.forename: Riyuan
authors.initials: R
authors.lastname: Zhang
authors.forename: Honghai
authors.initials: H
authors.lastname: Li
authors.forename: Hongfei
authors.initials: H
authors.lastname: Tong