Overexpression of p73 enhances cisplatin-induced apoptosis in HeLa cells.
To examine a possible synergistic role for p73 and cisplatin (cis-diamminedichloroplatinum II) in HeLa cells with a nonfunctional p53 protein, we established stable HeLa/p73 clones using a tetracycline inducible eukaryotic expression vector. The HeLa/p73 clones were not characterized by changes in growth or morphology. Cell death analysis, however, indicated a greater sensitivity to cisplatin in the p73-overexpressed HeLa cells than determined for the non-induced HeLa cells. This increased sensitivity seems to affect an induction of a sub-G1 population as assessed from flow cytometry analysis. The increased sub-G1 population may, in turn, result from a reduction of cyclin D1 and B1 expression by cisplatin in the presence of p73. Hoechest staining indicated an increased number of dead cells in the p73-induced cells compared to the non-induced cells. Poly ADP-ribose polymerase (PARP) cleavage was shown to be distinct in the p73-overexpressed cells compared to non-induced cells, which suggests that p73 modulates the cisplatin-induced apoptosis. Therefore, a synergistic effect of p73 and cisplatin to induce apoptosis could lead to new treatment for some types of human cancers.
Kim
Keun-Cheol
KC
Division of Life Sciences, College of Natural Sciences, Kangwon National University, Chuncheon 200-701, Korea. kckim@kangwon.ac.kr
Jung
Chul-Soo
CS
Choi
Kyung-Hee
KH
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology*; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D019938:Cyclin D1 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016147:Genes, Tumor Suppressor; D006367:HeLa Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D000970:Antineoplastic Agents; C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; D002945:Cisplatin