Skip to main content
SpringerLink
Log in

Chemosensitivity of human MCF-7 breast cancer cells to diastereoisomeric diaqua(1,2-diphenylethylenediamine) platinum(II) sulfates and specific platinum accumulation

  • Original Articles
  • Intracellular accumulation, Cisplatinum analogues, MCF-7 cells
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Summary

Cisplatin, raceme-diaqua[1,2-bis(4-fluorophenyl)ethylenediamine]platinum(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 μM), 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Andrews PA, Sriharsha V, Mann SC, Howell SB (1988)cis-Diamminedichloroplatinum(II) accumulation in sensitive and resistant human ovarian carcinoma cells. Cancer Res 48:68–73

    Google Scholar 

  2. Bernhardt G, Reile H, Birnböck H, Spruß T, Schönenberger H (1992) Standardized kinetic microassay to quantitate differential chemosensitivity based on proliferative activity. J Cancer Res Clin Oncol 118:35–43

    Google Scholar 

  3. Bernhardt G, Spruß T, Rustler M (1992) Comparison of MCF-7 and ZR-75-1 cell lines as models for studying hormone-dependent human breast cancer in nude mice. In: Fiebig HH, Berger DP (eds) Immunodeficient mice in oncology. Karger, Basel (in press)

    Google Scholar 

  4. Boyer RF (1986) Modern experimental biochemistry. Benjamin Cummings, Menlo Park, California, pp 437–446, 479–488

    Google Scholar 

  5. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Google Scholar 

  6. Brown DB, Khokhar AR, Hacker MP, McCormack JJ (1982) Synthesis and antitumor activity of platinum complexes containing neutral and protonated amino-olefin ligands. Inorg Chim Acta 67: 45–52

    Google Scholar 

  7. Brown DB, Khokhar AR, Hacker MP, Lokys L, Burchenal JH, Newman RA, McCormack JJ, Frost D (1982) Synthesis and antitumor activity of new platinum complexes. J Med Chem 25: 952–956

    Google Scholar 

  8. Byfield JE, Calabro-Jones PM (1981) Carrier-dependent and-independent transport of anticancer alkylating agents. Nature 294: 281–283

    Google Scholar 

  9. Fichtinger-Schepman AMJ, Oosterom AT van, Lohman PHM, Berends F (1987)cis-Diamminedichloroplatinum(II)-induced DNA adducts in peripheral leukocytes from seven cancer patients: quantitative immunochemical detection of the adduct induction and removal after a single dose ofcis-diamminedichloroplatinum(II). Cancer Res 47:3000–3004

    Google Scholar 

  10. Gale GR, Morris CR, Atkins LM, Smith AB (1973) Binding of an antitumor platinum compound to cells as influenced by physical factors and pharmacologically active agents. Cancer Res 33: 813–818

    Google Scholar 

  11. Gulotti M, Pasini A, Ugo R, Filippeschi S, Marmonti L, Spreafico F (1984) Enantiomeric cisplatin analogues: an investigation on their activity towards tumors in mice. Inorg Chim Acta 91:223–227

    Google Scholar 

  12. Hay RJ (1988) The seed stock concept and quality control for cell lines. Anal Biochem 171:225–237

    Google Scholar 

  13. Hydes PC (1984) Synthesis and testing of platinum analogues — an overview. In: Hacker MP, Douple EB, Krakoff IH (eds) Platinum coordination complexes in cancer chemotherapy. Martinus Nijhoff, Boston, pp 216–227

    Google Scholar 

  14. Karl J, Gust R, Spruss T, Schneider MR, Schönenberger H, Engel J, Wrobel K-H, Lux F, Trebert Haeberlin S (1988) Ring-substituted [1,2-bis(4-hydroxyphenyl)ethylenediamine]dichloroplatinum(II) complexes: compounds with a selective effect on the hormone-dependent mammary carcinoma. J Med Chem 31:72–83

    Google Scholar 

  15. Koch M, Bernhardt G (1991) Differential accumulation of stereoisomeric [1,2-bis(fluorophenyl)ethylenediamine]platinum(II) complexes by human breast cancer cells in vitro. J Cancer Res Clin Oncol 117 (Suppl 3):104

    Google Scholar 

  16. Köpf-Maier P, Köpf H, Neuse EW (1984) Ferricenium complexes: a new type of water soluble antitumor agent. J Cancer Res Clin Oncol 108:336–340

    Google Scholar 

  17. Lux F, Trebert-Haeberlin S, Erhardt W (1986) Neutronenaktivierungsanalytische Bestimmung des Chromgehaltes von Laboratoriumskaninchen-Skelettmuskel. Fresenius Z Anal Chem 323: 833–838

    Google Scholar 

  18. Müller R, Gust R, Jennerwein M, Reile H, Laske R, Krischke W, Bernhardt G, Spruss T, Engel J, Schönenberger H (1989) Tumor-inhibiting [1,2-bis(fluorophenyl)ethylenediamine]platinum(II) complexes: I. Synthesis. Eur J Med Chem 24:341–348

    Google Scholar 

  19. Nicolini M (ed) (1988) Platinum and other metal coordination compounds in cancer chemotherapy. Martinus Nijhoff, Boston

    Google Scholar 

  20. Noji M, Gohchi Y, Kidani Y (1984) Preparation of antitumor platinum(II) complexes of 1,2-diphenylethylenediamine isomers and their interaction with DNA and its purine moieties. Chem Biol Interact 51:37–48

    Google Scholar 

  21. Pinto AL, Lippard SJ (1985) Binding of the antitumor drugcis-diamminedichloroplatinum(II) (cisplatin) to DNA. Biochim Biophys Acta 780:167–180

    Google Scholar 

  22. Reed E, Kohn KW (1990) Platinum analogues. In: Chabner BA, Collins JM (eds) Cancer chemotherapy, principles and practice. J.B. Lippincott, Philadelphia, pp 465–490

    Google Scholar 

  23. Reile H, Birnböck H, Bernhardt G, Spruß T, Schönenberger H (1990) Computerized determination of growth kinetic curves and doubling times from cells in microculture. Anal Biochem 187: 262–267

    Google Scholar 

  24. Reile H, Müller R, Gust R, Laske R, Krischke W, Bernhardt G, Spruß T, Jennerwein M, Engel J, Seeber S, Osieka R, Schönenberger H (1990) Tumor-inhibiting [1,2-bis(fluorophenyl)ethylenediamine]platinum(II) complexes: II. Biological evaluation — in vitro studies on the P388 D1 leukemia cell line. Arch Pharm (Weinheim) 323:133–140

    Google Scholar 

  25. Reile H, Spruß T, Müller R, Gust R, Bernhardt G, Schönenberger H (1990) Tumor-inhibiting [1,2-bis(fluorophenyl)ethylenediamine]dichloroplatinum(II) complexes: III. Evaluation of mammary tumor-inhibiting properties. Arch Pharm (Weinheim) 323:301–306

    Google Scholar 

  26. Safirstein R, Miller P, Guttenplan JB (1984) Uptake and metabolism of cisplatin by rat kidney. Kidney Int 25:753–758

    Google Scholar 

  27. Schneider MR, Schiller C-D, Humm A, Spruß T, Schönenberger H, Amselgruber W, Sinowat F (1989) [1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]dichloroplatinum(II): an endocrineactive platinum complex with a specific prostatic tumor-inhibiting activity. Prostate 15:135–148

    Google Scholar 

  28. Soule HD, Vazques J, Long A, Albert S, Brennan M (1973) A human cell line from a pleural effusion derived from a breast carcinoma. J Natl Cancer Inst 51:1409–1416

    Google Scholar 

  29. Spruß T, Gust R, Müller R, Engel J, Schönenberger H (1990) Mammary tumor-inhibiting properties of the (S,S)-configurated [1,2-bis(4-hydroxyphenyl)ethylenediamine]dichloroplatinum(II) complex. Arch Pharm (Weinheim) 323:99–102

    Google Scholar 

  30. Spruß T, Bernhardt G, Schickaneder E, Schönenberger H (1991) Different response of murine and human mammary tumor models to a series of diastereoisomeric [1,2-bis(difluorophenyl)ethylenediamine]dichloroplatinum(II) complexes. J Cancer Res Clin Oncol 117:435–443

    Google Scholar 

  31. Staquet MJ, Byar DP, Green SB, Rozencweig 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 67:753–765

    Google Scholar 

  32. Trebert-Haeberlin S, Lux F, Karl J, Spruß T, Schönenberger H (1987) Determination of platinum and biologically important trace elements in structure-activity relationship studies on platinum-containing anti-cancer drugs. Special procedures for removing32P as well as for the estimation of99Mo and199Au. J Radioanal Nucl Chem 113:461–467

    Google Scholar 

  33. Wappes B, Jennerwein M, Angerer E von, Engel J, Schönenberger H, Brunner H, Schmidt M, Berger M, Schmähl D, Seeber S (1984) The tumor-inhibiting effect of isomeric dichloro(diphenylethylenediamine)platinum(II) complexes. J Cancer Res Clin Oncol 107:15–20

    Google Scholar 

  34. Williams PD, Hottendorf GH (1985) Effect of cisplatin on organic ion transport in membrane vesicles from rat kidney cortex. Cancer Treat Rep 69:875–880

    Google Scholar 

  35. Wilson AP (1986) Cytotoxicity and viability assays. In: Freshney RI (ed) Animal cell culture, a practical approach. IRL Press, Oxford Washington D.C., p 191

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut für Pharmazie, Universität Regensburg, Sonderforschungsbereich 234, Universitätsstraße 31, W-8400, Regensburg, Germany

    Herta Reile, Günther Bernhardt, Marion Koch & Helmut Schönenberger

  2. Institut für Radiochemie der Technischen Universität München, Walther-Meißner-Straße 3, W-8046, Garching, Germany

    Michael Hollstein & Franz Lux

Authors
  1. Herta Reile
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Günther Bernhardt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marion Koch
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Helmut Schönenberger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michael Hollstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Franz Lux
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This work was supported by the Deutsche Forschungsgemeinschaft and the Matthias Lackas Stiftung für Krebsforschung. Financial support was also provided by the Fonds der Chemischen Industrie

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reile, H., Bernhardt, G., Koch, M. et al. Chemosensitivity of human MCF-7 breast cancer cells to diastereoisomeric diaqua(1,2-diphenylethylenediamine) platinum(II) sulfates and specific platinum accumulation. Cancer Chemother. Pharmacol. 30, 113–122 (1992). https://doi.org/10.1007/BF00686402

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00686402

Keywords

Search

Navigation