Comparison of cytotoxicity and cell kinetic perturbations of 5 platinum compounds in gynecologic cancer cell-lines.

New platinum derivatives were synthesized to overcome problems of cisplatin resistance and nephrotoxicity. Five platinum derivatives were evaluated by using the ATP chemosensitivity assay and flow cytometry in a panel of 10 human gynecologic cancer cell lines: AE7, ECC1, HEC1A, HEC1B, AN3, BG1, CAOV3, SKOV3, SKUT1B and ME180. Five platinum derivatives and their referenced concentrations (X) were: Cisplatin (DDP) 2.5 mug/ml (8.3 muM), Carboplatin (CARBO) 28 mug/ml (75.5 muM), Tetraplatin (TETRA) 2 mug/ml (4.4 muM), 254S at 5 mug/ml (16.5 muM) and NK121 at 5 mug/ml (11.4 muM). Drug exposure was performed at 0, 0.1, 0.2, 0.5, 1, 2 and 5 X for 90 minutes. The ATP chemosensitivity assay was performed on day 7 as previously described. Cell samples were taken at 0, 24, 48, 72, 96 and 168 h timepoints for flow cytometry. Mean IC50s were: DDP 29.1+/-17.4 muM, 254S 18.2+/-6.6 muM, NK121 13.7+/-5.7 muM, CARBO 120.8+/-37.8 muM, and TETRA 30.8+/-20.7 muM. Both 254S and NK121 offered significant improvement of potency over DDP (p=0.02, 0.05 respectively). Similarly, Fell cycle kinetic studies revealed that both 254S and NK121 induced significantly more S and G2 blocks than DDP (p<0.02). Thus, from the chemo-sensitivity and cell kinetic standpoints, both NK121 and 254S appeared more potent and deserve further investigation.