title: Guggulsterone-induced apoptosis in cholangiocarcinoma cells through ROS/JNK signaling pathway.
abstract: Cholangiocarcinoma (CCA), the most common biliary tract malignancy, is arising from the bile duct epithelium with the global significantly increased morbidity and mortality. Here, we showed the effect of guggulsterone, a steroid found in the resin of the guggul plant, on human HuCC-T1 and RBE CCA cells. Exposure to various concentrations of guggulsterone for multiple action time resulted in significant apoptosis in the CCA cells via activating both extrinsic and intrinsic pathways. Furthermore, we demonstrated that the apoptosis of CCA cells was induced by Reactive oxygen species (ROS) mediated JNK signaling pathway. Consistently, inhibition of JNK activity, overexpression of JBD, its binding protein or reduction of ROS by overexpression of catalase, all decreased apoptotic cells. Our results also revealed that guggulsterone-induced apoptosis was coupled with endoplasmic reticulum stress (ERS) in CHOP-dependent pathway. Downregulation of CHOP instead of other ERS markers could inhibit CCA cell apoptosis. Taken together, our results showed that guggulsterone could induce apoptosis of human CCA cells through ROS/JNK signaling pathway, indicating that guggulsterone could be important for the clinical therapy of CCA.
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Anhui Medical University Hefei, Anhui, P. R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhong
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Anhui Medical University Hefei, Anhui, P. R. China.
authors.forename: Zhu-Ting
authors.initials: ZT
authors.lastname: Tong
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Anhui Medical University Hefei, Anhui, P. R. China.
authors.forename: Lu-Lu
authors.initials: LL
authors.lastname: Fan
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Anhui Medical University Hefei, Anhui, P. R. China.
authors.forename: Li-Xia
authors.initials: LX
authors.lastname: Zha
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Anhui Medical University Hefei, Anhui, P. R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Anhui Medical University Hefei, Anhui, P. R. China.
authors.forename: Meng-Qun
authors.initials: MQ
authors.lastname: Yao
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Anhui Medical University Hefei, Anhui, P. R. China.
authors.forename: Kang-Sheng
authors.initials: KS
authors.lastname: Gu
authors.affiliation: Department of Obstetrics and Gynecology, Reproductive Medicine Center, The First Affiliated Hospital, Anhui Medical University Hefei, Anhui, P. R. China.
authors.forename: Yun-Xia
authors.initials: YX
authors.lastname: Cao
keywords: CCA; ERS; Guggulsterone; JNK; apoptosis