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. 1991 Sep;117(5):435–443. doi: 10.1007/BF01612764

Different response of murine and human mammary tumour models to a series of diastereoisomeric [1,2-bis(difluorophenyl) ethylenediamine]dichloroplatinum(II) complexes

Thilo Spru\ 1, Günther Bernhardt 1,✉, Edith Schickaneder 1, Helmut Schönenberger 1
PMCID: PMC12201095  PMID: 1890139

Abstract

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-difiuorosubstituted 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 unam-biguously identified [1,2-bis(2,4-difluorophenyl)ethyle-nediamine]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.

Key words: Cisplatin analogues; P388 murine leukemia; MXT mouse mammary tumours; MCF-7, MDA-MB-231 human breast cancer cell lines; Aberrant response

Abbreviations

PBS

phosphate-buffered saline

PEG

polyethlyeneglycol

References

  1. Angerer Ev, Birnböck H, Knebel N (1989) Platinum complexes with a selective action on estrogen receptor-positive mammary tumors. Anti-Cancer Drug Design 4:21 [PubMed] [Google Scholar]
  2. Birnböck H (1988) Untersuchungen zur Pharmakokinetik des Zindoxifens und zur Wirkung von Inhibitoren der Steroidsulfatase an hormonabhÄngigen Tumoren. Dissertation, Regensburg
  3. Cailleau R, Young R, Olivé M, Reeves WJ (1974) Breast tumor cell lines from pleural effusions. J Natl Cancer Inst 53:661 [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chabner BA (1990) In defense of cell-line screening. J Natl Cancer Inst 82:1083 [DOI] [PubMed] [Google Scholar]
  5. Danguy A, Kiss R, Leclerq G, Heuson C, Pasteels JL (1986) Morphology of MXT mouse mammary tumors. Correlation with growth characteristics and hormone sensitivity. Eur J Clin Oncol 22:69 [DOI] [PubMed] [Google Scholar]
  6. Dawe CJ, Potter M (1957) Lymphocytic leukemia P 388 of the DBA/2 mouse. Am J Pathol 33:603 [Google Scholar]
  7. Driscoll JS (1984) The preclinical drug research program of the National Cancer Institute. Cancer Treat Rep 68:63 [PubMed] [Google Scholar]
  8. Gillies RJ, Didier N, Denton M (1986) Determination of cell number in monolayer cultures. Anal Biochem 159:109 [DOI] [PubMed] [Google Scholar]
  9. Goldin A, Venditti JM, Humphreys SR, Mantel N (1958) Quantitative evaluation of chemotherapeutic agents against advanced leukemia in mice. J Natl Cancer Inst 21:495 [PubMed] [Google Scholar]
  10. Johnson KJ (1990) Screening methods in antineoplastic drug discovery. J Natl Cancer Inst 82:1082 [DOI] [PubMed] [Google Scholar]
  11. Kerkvliet GJ (1990) Drug discovery screen adapts to changes. J Natl Cancer Inst. 82:1087 [DOI] [PubMed] [Google Scholar]
  12. Müller R, Gust R, Jennerwein M, Reile H, Laske R, Krischke W, Bernhardt G, Spru\ Th, Engel J, Schönenberger H (1989) Tumor Inhibiting [1,2-bis(fluorophenyl-ethylenediamine]platinum-(II) Complexes. Part I: Synthesis. Eur J Med Chem 24:341 [Google Scholar]
  13. Müller R, Schickaneder E, Jennerwein M, Reile H, Spru\ Th, Engel J, Schönenberger H (1991) Tumor inhibiting [1,2-bis(difluoro-phenyl)ethylenediamine]dichloroplatinum(II) complexes: part I. Synthesis. Arch Pharm (Weinheim) 324:115 [DOI] [PubMed] [Google Scholar]
  14. Orde HD vom, Reile H, Müller R, Gust R, Bernhardt G, Spru\ Th, Schönenberger H, Burgemeister T, Mannschreck A (1990) Tumor Inhibiting [1,2-bis(fluorophenyl)ethylenediamine]platinum-(II) complexes: V. Synthesis and evaluation of enantiomeric [1,2-bis-(4-fluorophenyl)ethylenediamine]dichloroplatinum(II) complexes. J Cancer Res Clin Oncol 116:434 [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Reile H, Müller R, Gust R, Laske R, Krischke W, Bernhardt G, Spru\ Th, Jennerwein M, Engel J, Seeber S, Osieka R, Schönenberger H (1990a) Tumor inhibiting [1,2-bis(fluorophenyl)ethyl-enediamine]platinim(II) complexes: part II. Biological evaluation — in vitro studies on the P 388 D1 leukemia cell line. Arch Pharm (Weinheim) 323:133 [DOI] [PubMed] [Google Scholar]
  16. Reile H, Spru\ Th, Müller R, Gust R, Bernhardt G, Schönenberger H, Engel J (1990b) Tumor inhibiting [1,2-bis(fluorophenyl)eth-ylenediamine]dichloroplatin(II) complexes (III). Evaluation of mammary tumor inhibiting properties. Arch Pharm (Weinheim) 323:301 [DOI] [PubMed] [Google Scholar]
  17. Schneider MR, Ball H, Schönenberger H (1985) Acetoxy substituted 1,1,2-triphenylbut-1-enes with antiestrogenic and mammary tumor inhibiting properties. J Med Chem 28:1880 [DOI] [PubMed] [Google Scholar]
  18. Schneider MR, Michna H, Nishino Y, El Etreby MF (1989) Antitumor activity of the progesterone antagonists ZK 98.299 and RU 38.486 in the hormone-dependent MXT mammary tumor model of the mouse and the DMBA- and MNU-induced mammary tumor models of the rat. Eur J Cancer Clin Oncol 25:691 [DOI] [PubMed] [Google Scholar]
  19. Schönenberger H, Kranzfelder G, Hoffmann E, Egginger G, Schmitt H, Taneja AK (1976) Experimentelle Chemotherapie des Mammakrebses. Pharmazie 31:590 [PubMed] [Google Scholar]
  20. Schönenberger H, Gust R, Karl J, Spru\ Th, Schneider MR, Hartmann RW, Batzl Ch, Schertl S, Engel J, Lux F, Trebert-Haeberlin S (1989) Rezeptorgebundene Chemotherapie in Antiöstrogene in Forschung und Klinik, Reihe Aktuelle Onkologie 46, Zuckschwerdt Verlag, München [Google Scholar]
  21. Silvestrini R, Sanfilippo O, Daidone MG (1983) In: Dendy PP, Hill BT (eds) Human tumor drug sensitivity testing in vitro. Academic Press, New York, p 281 [Google Scholar]
  22. Soule HD, Varques J, Long A, Albert S, Brennan MJ (1973) A human cell line from a pleural effusion derived from a breast carcinoma. J Natl Cancer Inst 51:1409 [DOI] [PubMed] [Google Scholar]
  23. Staquet MJ, Byar DP, Green SB, Rozenczweig M (1983) Clinical predictivity of transplantable tumor systems in the selection of new drugs for solid tumors: rationale for a three-stage strategy. Cancer Treat Rep 67:753 [PubMed] [Google Scholar]
  24. Watson C, Medina D, Clark JH (1977) Estrogen receptor characterization in a transplantable mouse mammary tumor. Cancer Res 37:3344 [PubMed] [Google Scholar]
  25. Watson C, Medina D, Clark JH (1980) Characterization of progesterone receptors, estrogen receptors, and estrogen (type II)-binding sites in the hormone-independent variant of the MXT-3590 mouse mammary tumor. Endocrinology 107:1432 [DOI] [PubMed] [Google Scholar]
  26. Wilson AP (1986) Cytotoxicity and viability assays. In: Freshney RI (ed) Animal cell culture: a practical approach. IRL, Eynsham, p 194 [Google Scholar]

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