title: Chemosensitivity of human MCF-7 breast cancer cells to diastereoisomeric diaqua(1,2-diphenylethylenediamine) platinum(II) sulfates and specific platinum accumulation.
abstract: Cisplatin, raceme-diaqua[1,2-bis(4-fluorophenyl)ethylenediamine]platinu m(II) sulfate (compound I), meso-diaqua[1,2-bis(4-fluorophenyl)ethylenediamine]-platinum(II) sulfate (compound II), and meso-diaqua[1,2-bis(2,6-dichloro-4- hydroxyphenyl)ethylenediamine]platinum(II) sulfate (compound III) were compared with regard to their effect on the MCF-7 breast cancer cell line in vitro. At equimolar concentrations (5 microM), cisplatin, compound I, and compound II were equiactive after 231 h drug exposure, whereas compound III was ineffective. Although compounds I and II showed markedly greater inactivation than did cisplatin after 6 h incubation with culture medium, compound I (but not compound II) exhibited antitumor activity equivalent to that of cisplatin when cells were exposed to the drugs for 6 h. Platinum measurements by neutron-activation analysis revealed that compound I was selectively and rapidly accumulated by MCF-7 cells, resulting in a high degree of DNA platination within the first few hours of drug exposure. However, when the drug-exposure period was long enough, platinum enrichment was not reflected in an overall difference in the cytotoxicity of compound I vs cisplatin. Nevertheless, compound I should be superior to cisplatin in vivo, provided that effective plasma levels can be maintained for about 6 h.
authors.affiliation: Universität Regensburg, Institut für Pharmazie, FRG.
authors.forename: H
authors.initials: H
authors.lastname: Reile
authors.forename: G
authors.initials: G
authors.lastname: Bernhardt
authors.forename: M
authors.initials: M
authors.lastname: Koch
authors.forename: H
authors.initials: H
authors.lastname: Schönenberger
authors.forename: M
authors.initials: M
authors.lastname: Hollstein
authors.forename: F
authors.initials: F
authors.lastname: Lux
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002945:Cisplatin / Q000493:pharmacokinetics / Q000494:pharmacology; D003470:Culture Media; D004273:DNA, Neoplasm / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D004355:Drug Stability; D006801:Humans; D007700:Kinetics; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D010984:Platinum / Q000493:pharmacokinetics; D013237:Stereoisomerism; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D003470:Culture Media; D004273:DNA, Neoplasm; D009944:Organoplatinum Compounds; D010984:Platinum; D002945:Cisplatin