Induction of apoptosis by cisplatin and its effect on cell cycle-related proteins and cell cycle changes in hepatoma cells

Cancer Lett. 2002 Jan 10;175(1):27-38. doi: 10.1016/s0304-3835(01)00720-0.

Abstract

We investigated cisplatin-induced apoptosis and the effects on cell cycle-related proteins and cell cycle changes. Two human hepatoma cell lines, HepG2 (with wild-type p53) and Hep3B (with deleted p53), were treated with different concentrations of cisplatin. Cisplatin induced apoptosis in both cell lines as assessed by cell morphology, DNA fragmentation analysis,TdT-mediated dUTP nick end labeling assay and flow cytometry. HepG2 cells were more sensitive to cisplatin than Hep3B. Low-dose cisplatin induced a transient G(1) arrest, S phase block and upregulation of p53 and p21(WAF1/CIP1) expression in HepG2, but not in Hep3B cells. With cisplatin at a high dose, both cell lines underwent apoptosis that was accompanied by downregulation of p27(KIP1) and Bcl-x(L). In HepG2, upregulation of p53 and p21(WAF1/CIP1) was observed before apoptosis occurred, suggesting that cisplatin-induced apoptosis in HepG2 might be p53-dependent. Expression of Fas was also increased following cisplatin treatment in HepG2. However, there was no induction of p53, p21(WAF1/CIP1) and Fas observed in Hep3B cells. In conclusion, cisplatin induced apoptosis in hepatoma cells via both p53-dependent and -independent pathways.

MeSH terms

  • Actins / genetics
  • Apoptosis / drug effects*
  • Blotting, Western
  • Carcinoma, Hepatocellular / pathology*
  • Cell Cycle / drug effects*
  • Cell Cycle Proteins / genetics*
  • Cisplatin / toxicity*
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / genetics
  • DNA Fragmentation
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • In Situ Nick-End Labeling
  • Kinetics
  • Liver Neoplasms / pathology*
  • Polymerase Chain Reaction
  • Tumor Cells, Cultured
  • fas Receptor / genetics

Substances

  • Actins
  • CDKN1A protein, human
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • fas Receptor
  • Cisplatin