Different response of murine and human mammary tumour models to a series of diastereoisomeric [1,2-bis(difluorophenyl) ethylenediamine]dichloroplatinum(II) complexes.
A series of isomeric [1,2-bis(difluorophenyl) ethylenediamine]dichloroplatinum(II) complexes and cisplatin were tested on the P388 leukemia and on the murine hormone-independent MXT (M3.2) OVEX and the ovarian-hormone-dependent MXT (M3.2) mammary carcinoma for evaluating antineoplastic activity against breast cancer in vivo. Although these results were heterogeneous, a trend to the 2,6-difluorosubstituted compound as the most active platinum complex was observed. For the development of a large-scale in vitro screening method on human breast cancer cell lines, cell number, [3H]thymidine incorporation, and crystal violet staining were evaluated as parameters for end-point determination. Chemosensitivity testing on the human breast cancer cell lines MDA-MB-231 and MCF-7 unambiguously identified [1,2-bis(2,4-difluorophenyl)ethylenediamine]dichloroplatinum(II) as the complex with the highest activity in the crystal violet micro-assay. In equimolar concentration this compound was superior to cisplatin on both cell lines. The analysis of the conflicting results of this study indicates that murine mammary carcinomas are most probably unrealistic and inappropriate models for the screening of cytotoxic platinum complexes with potential activity on human breast cancer.
Spruss
T
T
Universität Regensburg, Institut für Pharmazie, Federal Republic of Germany.
Bernhardt
G
G
Schickaneder
E
E
Schönenberger
H
H
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002945:Cisplatin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005029:Ethylenediamines / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007941:Leukemia P388 / Q000188:drug therapy / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000473:pathology; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D005029:Ethylenediamines; D009944:Organoplatinum Compounds; D002945:Cisplatin