Anordrin Eliminates Tamoxifen Side Effects without Changing Its Antitumor Activity.
Sci Rep
; 7: 43940, 2017 03 07.
Article
em En
| MEDLINE
| ID: mdl-28266626
ABSTRACT
Tamoxifen is administered for estrogen receptor positive (ER+) breast cancers, but it can induce uterine endometrial cancer and non-alcoholic fatty liver disease (NAFLD). Importantly, ten years of tamoxifen treatment has greater protective effect against ER+ breast cancer than five years of such treatment. Tamoxifen was also approved by the FDA as a chemopreventive agent for those deemed at high risk for the development of breast cancer. The side effects are of substantial concern because of these extended methods of tamoxifen administration. In this study, we found that anordrin, marketed as an antifertility medicine in China, inhibited tamoxifen-induced endometrial epithelial cell mitosis and NAFLD in mouse uterus and liver as an anti-estrogenic and estrogenic agent, respectively. Additionally, compared with tamoxifen, anordiol, the active metabolite of anordrin, weakly bound to the ligand binding domain of ER-α. Anordrin did not regulate the classic estrogen nuclear pathway; thus, it did not affect the anti-tumor activity of tamoxifen in nude mice. Taken together, these data suggested that anordrin could eliminate the side effects of tamoxifen without affecting its anti-tumor activity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tamoxifeno
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Neoplasias do Endométrio
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Antineoplásicos Hormonais
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Anticoncepcionais Orais Sintéticos
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Hepatopatia Gordurosa não Alcoólica
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Norandrostanos
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2017
Tipo de documento:
Article