Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 21, 2015; 21(47): 13277-13287
Published online Dec 21, 2015. doi: 10.3748/wjg.v21.i47.13277
Guggulsterone induces apoptosis of human hepatocellular carcinoma cells through intrinsic mitochondrial pathway
Juan-Juan Shi, Xiao-Li Jia, Mei Li, Ning Yang, Ya-Ping Li, Xin Zhang, Ning Gao, Shuang-Suo Dang
Juan-Juan Shi, Xiao-Li Jia, Mei Li, Ning Yang, Ya-Ping Li, Xin Zhang, Ning Gao, Shuang-Suo Dang, Department of Infectious Diseases, the Second Affiliated Hospital of Medical School of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
Author contributions: Shi JJ, Jia XL and Dang SS designed the research; Shi JJ, Li M, Yang N, Li YP, Zhang X and Gao N performed the research; Shi JJ, Yang N and Li YP analyzed the data; and Shi JJ wrote the paper.
Supported by Science and Technology Foundation of Shaanxi Province, China, No. 2007K16-07(9).
Institutional review board statement: No human or animal subjects in the study.
Institutional animal care and use committee statement: Animals were not used in the study.
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Xiao-Li Jia, PhD, Department of Infectious Diseases, the Second Affiliated Hospital of Medical School of Xi’an Jiaotong University, No. 157 Xi’wu Road, Xi’an 710004, Shaanxi Province, China. drjxl@163.com
Telephone: +86-29-87679688 Fax: +86-29-87679688
Received: April 29, 2015
Peer-review started: May 8, 2015
First decision: July 19, 2015
Revised: August 24, 2015
Accepted: October 17, 2015
Article in press: October 20, 2015
Published online: December 21, 2015
Processing time: 230 Days and 3.8 Hours
Abstract

AIM: To investigate the effects of guggulsterone on the proliferation and apoptosis of human hepatoma HepG2 cells in vitro and relevant mechanisms.

METHODS: Human hepatocellular carcinoma HepG2 cells and normal human liver L-02 cells were treated with different concentrations of guggulsterone (5-100 μmol/L) for 24-72 h. Cell proliferation was tested by MTT assay. Cell cycle and apoptosis were investigated using flow cytometry (FACS). Bcl-2 and Bax mRNA and protein expression was detected by real-time PCR and Western blot, respectively. TGF-β1, TNF-α, and VEGF contents were determined by ELISA.

RESULTS: Guggulsterone significantly inhibited HepG2 cell proliferation in a dose- and time-dependent manner. FACS showed that guggulsterone arrested HepG2 cell cycle at G0/G1 phase. Guggulsterone induced apoptosis was also observed in HepG2 cells, with 24.91% ± 2.41% and 53.03% ± 2.28% of apoptotic cells in response to the treatment with 50 μmol/L and 75 μmol/L guggulsterone, respectively. Bax mRNA and protein expression was significantly increased and Bcl-2 mRNA and protein expression was decreased. ELISA analysis showed that the concentrations of TGF-β1 and VEGF were significantly decreased and TNF-α concentration was increased.

CONCLUSION: Guggulsterone exerts its anticancer effects by inhibiting cell proliferation and inducing apoptosis in HepG2 cells. Guggulsterone induces apoptosis by activation of the intrinsic mitochondrial pathway.

Keywords: Guggulsterone; Hepatocellular carcinoma cells; Apoptosis; Cell cycle; Mitochondrial pathway

Core tip: Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer and the second leading cause of tumor mortality worldwide. Guggulsterone (GS) is a phytosterol extracted from the gum resin of guggul plants, and its pro-apoptotic effect has been found to play a pivotal role in its anti-carcinogenic mechanisms. In this study, we investigated the anticancer effects of GS-induced apoptosis in human HCC cells and the underlying molecular mechanisms. Our results demonstrated that GS induced HepG2 cell apoptosis through regulating Bcl-2 and Bax expression levels.