Abstract
We have investigated the modifying influence of 17-beta oestradiol (E2), on the cytotoxicity of methotrexate (MTX) towards two cell lines derived from human breast carcinoma. E2 (10(-7) M-10(-6) M) significantly reduced the antimetabolic effects of the drug towards an E2 non-responsive cell line, MDA-MB-436, whilst potentiating the action of MTX in an E2 responsive line, MCF-7. Similarly, E2 (10(-6) M) partially reversed the anti-proliferative effects of MTX in the MDA-MB-436 line and potentiated growth inhibition in the E2 responsive cells. This potentiation was not observed if E2 was replaced by the less biologically active alpha-isomer. In both cell lines pharmacological concentrations of the E2 reduced intracellular levels of MTX achieved during a 48 h treatment period. The latter finding is consistent with the ability of E2 to protect MDA-MB-436 cells from the action of MTX. Potentiation of the effects of MTX towards MCF-7 cells occurs despite reduced intra-cellular drug levels.
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- Brunner K. W., Sonntag R. W., Alberto P., Senn H. J., Martz G., Obrecht P., Maurice P. Combined chemo- and hormonal therapy in advanced breast cancer. Cancer. 1977 Jun;39(6 Suppl):2923–2933. doi: 10.1002/1097-0142(197706)39:6<2923::aid-cncr2820390679>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
- Carter S. K. The interpretation of trials: combined hormonal therapy and chemotherapy in disseminated breast cancer. Breast Cancer Res Treat. 1981;1(1):43–51. doi: 10.1007/BF01807891. [DOI] [PubMed] [Google Scholar]
- Clarke R., Van den Berg H. W., Kennedy D. G., Murphy R. F. Reduction of the anti-metabolic and anti-proliferative effects of methotrexate by 17 beta-oestradiol in a human breast carcinoma cell line, MDA-MB-436. Eur J Cancer Clin Oncol. 1983 Jan;19(1):19–24. doi: 10.1016/0277-5379(83)90391-7. [DOI] [PubMed] [Google Scholar]
- Jakesz R., Smith C. A., Aitken S., Huff K., Schuette W., Shackney S., Lippman M. Influence of cell proliferation and cell cycle phase on expression of estrogen receptor in MCF-7 breast cancer cells. Cancer Res. 1984 Feb;44(2):619–625. [PubMed] [Google Scholar]
- Katzenellenbogen B. S., Norman M. J., Eckert R. L., Peltz S. W., Mangel W. F. Bioactivities, estrogen receptor interactions, and plasminogen activator-inducing activities of tamoxifen and hydroxy-tamoxifen isomers in MCF-7 human breast cancer cells. Cancer Res. 1984 Jan;44(1):112–119. [PubMed] [Google Scholar]
- Lippman M., Bolan G., Huff K. The effects of estrogens and antiestrogens on hormone-responsive human breast cancer in long-term tissue culture. Cancer Res. 1976 Dec;36(12):4595–4601. [PubMed] [Google Scholar]
- Page M. J., Field J. K., Everett N. P., Green C. D. Serum regulation of the estrogen responsiveness of the human breast cancer cell line MCF-7. Cancer Res. 1983 Mar;43(3):1244–1250. [PubMed] [Google Scholar]
- Pichon M. F., Milgrom E. Characterization and assay of progesterone receptor in human mammary carcinoma. Cancer Res. 1977 Feb;37(2):464–471. [PubMed] [Google Scholar]
- Shafie S., Brooks S. C. Characteristics of the dextran-coated charcoal assay for estradiol receptor in breast cancer preparations. J Lab Clin Med. 1979 Nov;94(5):784–798. [PubMed] [Google Scholar]
- Van den Berg H. W., Ball C. R. The effect of methylazoxymethanol acetate on DNA synthesis and cell proliferation of synchronous HeLa cells. Mutat Res. 1972 Dec;16(4):381–390. doi: 10.1016/0027-5107(72)90206-0. [DOI] [PubMed] [Google Scholar]
- Weichselbaum R. R., Hellman S., Piro A. J., Nove J. J., Little J. B. Proliferation kinetics of a human breast cancer line in vitro following treatment with 17beta-estradiol and 1-beta-D-arabinofuranosylcytosine. Cancer Res. 1978 Aug;38(8):2339–2342. [PubMed] [Google Scholar]