Cell death and DNA fragmentation induced by liposomal platinum(II) complex, L-NDDP in A2780 and A2780/PDD cells

The effect of cisplatin and its non-cross resistant analogue, liposomal cis-bis-neodecanoato-trans-R,R-1,2-diamiconocyclohexaneplatinum (II) (L-NDDP) on inducing internucleosomal DNA fragmentation and cell death was examined in A2780 and A2780/PDD cells. In A2780 cells, both drugs were markedly effective in inducing DNA fragmentation, whereas in A2780/PDD cells, only L-NDDP produced significant DNA fragmentation, in good correlation with the observed cytotoxicity. The endonuclease inhibitor (ATA) prevented the DNA fragmentation caused by high (30-60 microM) or low (3-10 microM) concentrations of each drug in A2780 cells. In contrast, the protein synthesis inhibitor (CHX) displayed only a significant inhibitory effect on the DNA fragmentation caused by low concentrations at 48 h post-treatment. These results indicate that there are at least two different pathways leading to both drugs induced-cell death depending on drug concentrations in this cell line.