Toxicity of cisplatin and its metabolites on ovarian cancer cells.

Abstract

Cisplatin (CP) is one of our most useful antineoplastic drugs. When CP is dissolved in human plasma, different metabolites are formed. We examined the interactions of CP and its metabolites, namely aquated CP (AP), monomethionine CP (MP), bismethionine CP (BP) and CP dissolved in plasma ultrafiltrate (UP) on the OV 2008 human ovarian cancer cell line. By clonogenic assays, cell survivals (%) with AP, CP, MP, BP and UP were 3.28 $\pm$ 0.73, 9.84 $\pm$ 0.99, 15.93 $\pm$ 1.11, 76.83 $\pm$ 2.13 and 13.11 $\pm$ 0.74, respectively. AP was the most cytotoxic species, and BP was the least cytotoxic species. Cellular platinum (ng/10$\sp6$ cells) accumulation after addition of 0.33 (#1), 1.6 (#2) and 2.5 (#3) mM of each species was:(UNFORMATTED TABLE OR EQUATION FOLLOWS)$$\vbox{\halign{#\hfil&&\enspace#\hfil\cr\lbrack Species\rbrack &CP &AP &MP &BP &UP\cr\cr \#1 &289$\pm$26 &1080$\pm$90 &138$\pm$5 &24$\pm$1 &187$\pm$26\cr \#2 &607$\pm$31 &4352$\pm$145 &372$\pm$8 &56$\pm$2 &498$\pm$69\cr \#3 &713$\pm$41 &6610$\pm$279 &710$\pm$8 &78$\pm$2 &711$\pm$96\cr}}$$(TABLE/EQUATION ENDS) There is a strong correlation between cytotoxicity of the platinum species and their cellular uptake (r = 0.997). Infrared spectroscopy (IR) was done on OV 2008 cells after one hour exposure to different concentrations of species. IR data suggest that MP induced more cellular changes than the other species. While bands of all CP metabolites attributed to the phosphate and amide II stretching indicate a frequency shift and intensity variation, those of methyl and methylene stretching vibrations of the cell membrane seem to be hardly affected. In conclusion, CP and its metabolites have different effects on OV 2008 cells.