title: Guggulsterone inhibits human cholangiocarcinoma Sk-ChA-1 and Mz-ChA-1 cell growth by inducing caspase-dependent apoptosis and downregulation of survivin and Bcl-2 expression.
abstract: Guggulsterone has recently been reported to demonstrate anti-tumor effects in a variety of cancers. The present study aims to investigate the biological roles and underlying mechanism of the action of guggulsterone in cholangiocarcinoma. The immortalized human cholangiocarcinoma Sk-ChA-1 and Mz-ChA-1 cell lines were treated with various concentrations of thetransisomer of guggulsterone, Z-guggulsterone. Cellular proliferation was determined using the XTT assay. The apoptotic status of cholangiocarcinoma cells was assessed by Hoechst 33258 staining, DNA fragmentation assay and ﬂow cytometry. Specific caspase inhibitor was used to explore the role of caspase in guggulsterone-induced apoptosis. A colorimetric assay was performed to measure the alterations of the activities of caspase-3, -8 and -9. Western blot analysis was used to detect the protein expression of survivin, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein and cleaved poly (adenosine diphosphate-ribose) polymerase (PARP). As revealed by the present data, guggulsterone significantly inhibited the growth of the two human cholangiocarcinoma cell lines by inducing cellular apoptosis. In addition, guggulsterone-induced apoptosis of cholangiocarcinoma cells was demonstrated to be partially inhibited by the caspase inhibitors z-VAD-fmk, z-LEHD-fmk and z-IETD-fmk, accompanied by the activation of caspases-3, -8 and -9, accumulation of cleaved PARP and decreased expression of survivin and Bcl-2. In conclusion, the present study demonstrated that guggulsterone was able to suppress the proliferation of cholangiocarcinoma by inducing caspase-dependent apoptosis and downregulating survivin and Bcl-2.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhong
authors.affiliation: Department of Neurology, Anhui Provincial Hospital, Hefei, Anhui 230001, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors.forename: Zhu-Ting
authors.initials: ZT
authors.lastname: Tong
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors.forename: Liu-Liu
authors.initials: LL
authors.lastname: Chen
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors.forename: Lu-Lu
authors.initials: LL
authors.lastname: Fan
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors.forename: Xia-Li
authors.initials: XL
authors.lastname: Zha
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
keywords: B-cell lymphoma 2; Survivin; apoptosis; caspase; cholangiocarcinoma; guggulsterone