Pro-Apoptotic Effects of Estetrol on Long-Term Estrogen-Deprived Breast Cancer Cells and at Low Doses on Hormone-Sensitive Cells.
Breast Cancer (Auckl)
; 13: 1178223419844198, 2019.
Article
em En
| MEDLINE
| ID: mdl-31205415
ABSTRACT
PURPOSE:
Postmenopausal women with estrogen receptor-positive breast cancers often respond initially to tamoxifen or aromatase inhibitor therapy. Resistance to these treatments usually develops within 12 to 18 months. Clinical studies have demonstrated that high-dose estrogen can induce regression of these endocrine-resistant tumors. However, side-effects of high-dose estradiol (E2) or diethylstilbestrol (DES) limit their usage. Estetrol (E4) is the most abundant estrogen during pregnancy and has a long half-life and a low potential for side-effects. Estetrol might then provide benefits similar to DES on tumor regression but with lesser toxicity.METHODS:
In this study, we systematically evaluated the effects of E4 on cell proliferation and apoptosis in wild-type MCF-7 and long-term estrogen-deprived (LTED) MCF-7 cells and compared its effects with E2 and estriol (E3).RESULTS:
Estetrol induced apoptosis in LTED cells but stimulated growth of MCF-7 cells at concentrations from 10-11 to 10-8 M. These effects of E4 are similar to those of E2 but require much higher doses. Differing from E2, E4 at 10-12 M induced apoptosis in MCF-7 cells and another pregnancy estrogen, E3, acted similarly. No antagonistic effect of E4 or E3 against E2 occurred when they were combined.CONCLUSIONS:
The pro-apoptotic effects of E4 and E3 on LTED cells and at low doses on MCF-7 cells indicate that these steroids could be used as therapeutic agents for endocrine-resistant or sensitive breast cancer.
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MEDLINE
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article