Discrepancy between cytotoxicity, platinum accumulation, and DNA platination in MCF-7 breast cancer cells treated with diaqua(1,2-diphenylethylenediamine) platinum(II) sulfates and cisplatin

Abstract

Cisplatin (cis), racemic-diaqua[1,2-bis(4-fluorophenyl)ethylenediamine]platinum(II) sulfate (r-4F-PtSO4), meso-diaqua[1,2-bis(4-fluorophenyl)ethylenediamine]platinum(II) sulfate (m-4F-PtSO4), and meso-diaqua[1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]platinum(II) sulfate (m-2,6Cl2-4OH-PtSO4) were compared with regard to their growth inhibitory effect on MCF-7 breast cancer cells. At concns. of 5 mM, cis, r-4F-PtSO4, and m-4F-PtSO4 were essentially equiactive, whereas m-2,6Cl2-4OH-PtSO4 was ineffective. Platinum measurements by neutron activation anal. showed that a 24-h treatment of the MCF-7 cells with r-4F-PtSO4 and m-4F-PtSO4 caused a 22.3- and 10.3-fold accumulation, resp., whereas the accumulation factors for cis (2.55) and m-2,6Cl2-4OH-PtSO4 (1.83) were very low. The comparison of DNA-assocd. platinum revealed a similar tendency. After 24 h of drug exposure, the base pair/a similar tendency. After 24 h of drug exposure, the base pair/platinum ratios were: 2.1.104 for r-4F-PtSO4, 3.7.104 for m-4F-PtSO4, 6.1.104 for cisplatin, and 8.1.104 for m-2,6Cl2-4OH-PtSO4. Thus, the grade of cytotoxicity was correlated neither with the extent of cellular platinum enrichment nor with the degree of genomic DNA platination.