RU486, a progestin and glucocorticoid antagonist, inhibits the growth of breast cancer cells via the progesterone receptor.
Abstract
The progestin and glucocorticoid antagonist RU486 was tested on the growth of several cell lines in culture. RU486 inhibited the growth of two progesterone receptor (RP) positive human breast cancer cell lines (MCF7 and T47D). The antiproliferative effect was dose dependent and its magnitude correlated with the RP content of the tested cells (T47D greater than estradiol-primed MCF7 greater than withdrawn MCF7). Cell growth inhibition was not prevented by the addition of dexamethasone, dihydrotestosterone, or estradiol, but the cells were rescued by low concentrations of the progestin R5020. RU486 had no effect on the growth of two RP negative human breast cancer cell lines and a rat fibroblast cell line. Moreover, RU486 had no progestin agonist activity in T47D cells when evaluated by measuring the 35S-labeling of two progestin-regulated proteins with mol wts of 48,000 and 250,000, but it totally prevented the induction of these two proteins by R5020. In conclusion, RU486 selectively inhibited the growth of human breast cancer cell lines with unoccupied RP sites and its effect was correlated with the RP concentration of these cells. We propose that RU486 is a RP-targeted drug of potential utility in breast cancer treatment.
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Use of ERT requires addition of progestins to counteract endometrial proliferation induced by estrogens, whereas both estrogens and progestins could increase risk of breast cancer.
“The use of ERT requires the addition of progestins to counteract the endometrial proliferation induced by estrogens, whereas both estrogens and progestins could increase the risk of breast cancer (5,318).”
From Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone (2003) · cites this paper as [318]
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- Authors
- BARDON, S., VIGKPN, F., CHALBOS, D., & ROCHEFORT, H.
- Affiliations
- Inserm (FR)
- ORCID
- CHALBOS, DANY
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1985-04
- Volume
- 60
- Issue
- 4
- Pages
- 692-697
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W1973759771
- Cited by
- 143
- References
- 28
- Citations by year
- 2026: 1 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 2 · 2017: 1 · 2016: 3 · 2014: 1 · 2013: 2 · 2012: 2
- FWCI
- 8.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Keywords
- RU486, mifepristone, progesterone receptor, breast cancer, antiproliferative activity, MCF-7 cells, T47D cells, R5020, glucocorticoid receptor antagonist, targeted cancer therapy
- MeSH terms
- Breast Neoplasms, Cell Division, Cell Line, Electrophoresis, Polyacrylamide Gel, Estrenes, Glucocorticoids, Humans, Neoplasm Proteins, Progestins, Receptors, Glucocorticoid, Receptors, Progesterone, Mifepristone
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