Molecular mechanisms of apoptosis in hepatocellular carcinoma cells induced by ethanol extracts of Solanum lyratum Thumb through the mitochondrial pathway

World J Gastroenterol. 2017 Feb 14;23(6):1010-1017. doi: 10.3748/wjg.v23.i6.1010.

Abstract

Aim: To explore the induction effects and mechanism of Solanum lyratum Thumb (ST) on human hepatocellular carcinoma SMMC-7721 cells through the mitochondrial pathway.

Methods: The experiments were conducted on three groups: an experimental group (with ST ethanol extracts' concentration being 2.5, 5 and 10 mg/L), a negative control group (with only nutrient solution, 0 mg/L ST ethanol extracts), and a positive control group (2.5 mg/L DDP). The inhibition rate of cell proliferation was checked by using the methyl thiazolyl tetrazolium method, and cell apoptosis was tested by TUNEL method. Furthermore, RT-PCR was used to examine mRNA expression of Fas, FasL, caspase-8, caspase-3, p53 and Bcl-2 genes.

Results: Compared with the negative control group, the inhibition and apoptosis rates of the experimental group with different concentrations of ST extracts on human hepatocellular carcinoma SMMC-7721 cells significantly increased (P < 0.05). Besides, the mRNA expression of FasL and Bcl-2 significantly decreased (P < 0.05) while the mRNA expression of Fas, caspase-8, caspase-3 and p53 increased significantly. When compared with the positive control group, the experimental groups with 5 mg/L ST ethanol extracts showed effects similar to the positive control group.

Conclusion: ST ethanol extracts induced the apoptosis of hepatocellular carcinoma SMMC-7721 cells through up-regulated Fas, caspase-8, caspse-3 and p53, and down-regulated FasL and Bcl-2 in the mitochondrial pathway.

Keywords: Solanum lyratum Thumb; cell apoptosis; hepatocellular carcinoma cell; mitochondrial pathway; molecular mechanism.

MeSH terms

  • Apoptosis / drug effects*
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / physiopathology*
  • Caspase 3
  • Caspase 8
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Down-Regulation
  • Drugs, Chinese Herbal / pharmacology*
  • Drugs, Chinese Herbal / therapeutic use
  • Ethanol / chemistry
  • Fas Ligand Protein / metabolism
  • Humans
  • In Situ Nick-End Labeling
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / physiopathology*
  • Mitochondria / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction / drug effects*
  • Solanum / chemistry*
  • Tumor Suppressor Protein p53 / metabolism
  • Up-Regulation
  • fas Receptor / metabolism

Substances

  • BCL2 protein, human
  • Drugs, Chinese Herbal
  • FAS protein, human
  • FASLG protein, human
  • Fas Ligand Protein
  • Proto-Oncogene Proteins c-bcl-2
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • fas Receptor
  • Ethanol
  • CASP3 protein, human
  • CASP8 protein, human
  • Caspase 3
  • Caspase 8