Abstract
A rapid assay system for measuring the potential of estrogenic drugs is introduced. Luciferase induction could be measured in estrogen-receptor-positive human MCF-7 breast cancer cells, which had been transfected with a novel luciferase reporter plasmid ERE luc. The minimal requirement was 1 h exposure to the inducing drug and 3.5 h of incubation after removal of the drug. The assay system was used to measure the stability of the drug diaqua-[1,2-bis (2,6-dichloro-4-hydroxyphenyl) ethylenediamine] platinum(II) sulfate, containing an estrogenic ligand and reactive platinum. Luciferase activity was observed only when the drug was in the culture medium and cells for short times, whereas the estrogenic ligand alone remained active. It is assumed that binding of the platinum moiety to macromolecular constituents of the culture or cells renders the drug inaccessible for binding to the estrogen receptor.
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References
Angerer von E, Holler E, Schönenberger H, Schönenberger R (1989) Antineoplastic drugs. In: Smith DF (ed) Handbook of steroisomers: therapeutic drugs. CRC, Boca Raton, FL, pp 247–284
Angerer von E, Knebel N, Kager M, Ganss B (1990) 1-(Aminoalkyl)-2-phenylindoles as novel pure estrogen antagonists. J Med Chem 33:2635–2640
Bednarski PJ, Trümbach B, Kratochwil NA, Schönenberger H (1992) Diamine ligand release from the cisplatin analogue [meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine] dichloroplatinum(II) in cell culture medium. J Med Chem 35:4479–4485
Bernges F, Holler E (1992) Ring-substituted diaqua(1,2-diphenyl-ethylenediamine) platinum(II) sulfate reacts with DNA through a dissociable complex. Eur J Biochem 208:573–579
Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein ultilizing the principle of protein-dye binding. Anal Biochem 72:248–254
Farr A, Roman A (1992) A pitfall of using a second plasmid to determine transfection efficiency. Nucleic Acids Res 20:920
Horwitz KB, McGuire WL (1978) Nuclear mechanisms of estrogen action. J Biol Chem 253:8185–8191
Karl J, Gust R, Spruß T, Schneider M, Schönenberger H, Engel J, Wrobel KH, 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
Kranzfelder G, Schneider M, Angerer E von, Schönenberger H (1980) Entwicklung neuer Antiöstrogene vom Typ des 3,3′-Dihydroxy-α,β-diäthylstilbens und ihre Prüfung am DMBA-induzierten hormonabhängigen Mammacarcinom der SD-Ratte. J Cancer Res Clin Oncol 97:167–175
Norman RE, Ranford JD, Sadler PJ (1992) Studies of platinum(II) methionine complexes: metabolites of cisplatin. Inorg Chem 31:877–888
Odenheimer B, Wolf W (1982) Reactions of cisplatin with sulfur-containing amino acids and peptides. I. Cysteine and glutathione. Inorg Chem Acta 66:L41-L43
Ott M-O, Sperling L, Herbomel P, Yaniv M, Weiss M (1984) Tissue-specific expression is conferred by a sequence from the 5′-end of the rat albumine gene. EMBO J 3:2505–2510
Rubin BL, Dorfman AS, Black L, Dorfman RJ (1951) Bioassay of estrogens using the mouse uterine response. Endocrinology 49:429–439
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Meyer, T., Koop, R., von Angerer, E. et al. A rapid luciferase transfection assay for transcription activation effects and stability control of estrogenic drugs in cell cultures. J Cancer Res Clin Oncol 120, 359–364 (1994). https://doi.org/10.1007/BF01247461
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DOI: https://doi.org/10.1007/BF01247461