Ginsenoside Rg3 inhibit hepatocellular carcinoma growth via intrinsic apoptotic pathway

World J Gastroenterol. 2011 Aug 21;17(31):3605-13. doi: 10.3748/wjg.v17.i31.3605.

Abstract

Aim: To investigate the anti-tumor function of ginsenoside Rg3 on hepatocellular carcinoma (HCC) in vitro and in vivo, and its mechanism.

Methods: Hep1-6 and HepG2 cells were treated by Rg3 in different concentrations (0, 50, 100 and 200 μg/mL) in vitro. After incubation for 0, 6, 12, 24 and 48 h, cell viability was measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. Apoptosis was identified by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling. Caspase-3 activity was measured by chromophore p-nitroanilide and flow cytometry. Bcl-2 family proteins were ascertained by Western-blotting. Mitochondria membrane potential was detected by 5, 5', 6' 6' - tetrachloro-1, 1', 3, 3' - tetraethylbenzimidazolylcarbocyanine iodide. Forty liver tumor-bearing C57Bl6 mice were divided randomly into 4 groups for intra-tumor injection of saline, ginsenoside Rg3, cyclophosphamide (CTX) and ginsenoside Rg3 + CTX combination.

Results: The survival time was followed up to 102 d. The mice in the Rg3 + CTX group showed significant increased survival time compared with those in the control group (P < 0.05). Rg3 could inhibit HCC cell proliferation and induce cell apoptosis in vitro in the concentration and time dependent manner. It also induced mitochondria membrane potential to decrease. Caspase-3 activation can be blocked by the inhibitor z-DEVD-FMK. Bax was up-regulated while Bcl-2 and Bcl-XL were down-regulated after Rg3 treatment.

Conclusion: Our data suggested that Rg3 alone or combined with CTX inhibited tumor growth in vivo and prolonged mouse survival time by inducing HCC cell apoptosis via intrinsic pathway by expression alterations of Bcl-2 family proteins.

Keywords: Apoptosis; Bcl-2 family proteins; Cyclophosphamide; Ginsenoside Rg3; Hepatocellular Carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Apoptosis / drug effects*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / physiopathology*
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cyclophosphamide / pharmacology
  • Cyclophosphamide / therapeutic use
  • Cysteine Proteinase Inhibitors / pharmacology
  • Female
  • Ginsenosides* / pharmacology
  • Ginsenosides* / therapeutic use
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / physiopathology*
  • Mice
  • Mice, Inbred C57BL
  • Oligopeptides / pharmacology
  • Random Allocation
  • Survival Rate

Substances

  • Antineoplastic Agents
  • Cysteine Proteinase Inhibitors
  • Ginsenosides
  • Oligopeptides
  • benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone
  • ginsenoside Rg3
  • Cyclophosphamide
  • Caspase 3