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

Lux, Franz and Hollstein, Michael and Reile, Herta and Bernhardt, Günther and Schönenberger, Helmut (1996) 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. BIOLOGICAL TRACE ELEMENT RESEARCH, 53 (1-3). pp. 113-128. ISSN 0163-4984, 1559-0720

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Abstract

Cisplatin (cis), raceme-diaqua[1,2-bis(4-fluorophenyl)ethylenedi amine]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-2,6Cl(2)-4OH-PtSO4) were compared with regard to their growth inhibitory effect on MCF-7 breast cancer cells. At concentrations of 5 mu M, cis, r-4F-PtSO4, and m-4F-PtSO4 were essentially equiactive, whereas m-2,6Cl(2)-4OH-PtSO4 was ineffective. Platinum measurements by neutron activation analysis 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, respectively, whereas the accumulation factors for cis (2.55) and m-2,6Cl(2)-4OH-PtSO4 (1.83) were very low. The comparison of DNA-associated platinum revealed a similar tendency. After 24 h of drug exposure, the base pair/platinum ratios were: 2.1 . 10(4) for r-4F-PtSO4, 3.7 . 10(4) for m-4F-PtSO4, 6.1 . 10(4) for cisplatin, and 8.1 . 10(4) for m-2,6Cl(2)-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.

Item Type: Article
Uncontrolled Keywords: NEUTRON-ACTIVATION ANALYSIS; INHIBITING <1,2-BIS(FLUOROPHENYL)ETHYLENEDIAMINE>PLATINUM(II) COMPLEXES; NOBLE-METALS; CHEMOSENSITIVITY; SEPARATION; CARCINOMA; BINDING; LINE; cisplatin analogs; MCF-7 cells; chemosensitivity; neutron activation analysis; intracellular platinum accumulation; platination of genomic DNA
Subjects: 600 Technology > 615 Pharmacy
Divisions: Chemistry and Pharmacy > Institute of Pharmacy > Alumni or Retired Professors > Prof. Schönenberger
Depositing User: Dr. Gernot Deinzer
Date Deposited: 05 Jul 2023 09:47
Last Modified: 05 Jul 2023 09:47
URI: https://pred.uni-regensburg.de/id/eprint/51659

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