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

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 G1 arrest, S phase block and upregulation of p53 and p21WAF1/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 p27KIP1 and Bcl-xL. In HepG2, upregulation of p53 and p21WAF1/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, p21WAF1/CIP1 and Fas observed in Hep3B cells. In conclusion, cisplatin induced apoptosis in hepatoma cells via both p53-dependent and -independent pathways. © 2002 Elsevier Science Ireland Ltd. All rights reserved.