title: Guggulsterone induces apoptosis of human hepatocellular carcinoma cells through intrinsic mitochondrial pathway.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Juan-Juan
authors.initials: JJ
authors.lastname: Shi
authors.affiliation: 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.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Jia
authors.affiliation: 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.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Ning
authors.initials: N
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Ning
authors.initials: N
authors.lastname: Gao
authors.affiliation: 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.
authors.forename: Shuang-Suo
authors.initials: SS
authors.lastname: Dang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011282:Pregnenediones / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; C000595707:BCL2 protein, human; D011282:Pregnenediones; D019253:Proto-Oncogene Proteins c-bcl-2; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051028:bcl-2-Associated X Protein; C023617:pregna-4,17-diene-3,16-dione
keywords: Apoptosis; Cell cycle; Guggulsterone; Hepatocellular carcinoma cells; Mitochondrial pathway