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.
Department of Thoracic/Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston.
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Han
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Ling
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Khokhar
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Perez-Soler
D000970:Antineoplastic Agents / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D003513:Cycloheximide / Q000633:toxicity; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007700:Kinetics; D008081:Liposomes; D009944:Organoplatinum Compounds / Q000633:toxicity*; D010051:Ovarian Neoplasms; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D009944:Organoplatinum Compounds; C054367:bis-neodecanoato-1,2-diaminocyclohexaneplatinum(II); D003513:Cycloheximide; D002945:Cisplatin