2. Academic Validation
  3. Anordrin Eliminates Tamoxifen Side Effects without Changing Its Antitumor Activity

Anordrin Eliminates Tamoxifen Side Effects without Changing Its Antitumor Activity

  • Sci Rep. 2017 Mar 7:7:43940. doi: 10.1038/srep43940.
Wenwen Gu 1,  Wenping Xu 2,  Xiaoxi Sun 3,  Bubing Zeng 2,  Shuangjie Wang 1,  Nian Dong 4,  Xu Zhang 1,  Chengshui Chen 4,  Long Yang 5,  Guowu Chen 3,  Aijie Xin 3,  Zhong Ni 6,  Jian Wang 1,  Jun Yang 1
Affiliations

Affiliations

  • 1 Key Laboratory of Contraception Regulation of National Population and Family Planning Commission, Shanghai Institute of Planned Parenthood Research, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 200032, China.
  • 2 Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East-China University of Science, and Technology, 130 Meilong Road, Shanghai, 200237, China.
  • 3 Obstetrics and Gynecology Hospital, Shanghai Ji Ai Genetics and IVF Institute, Institute of Reproduction and Development, Fudan University, Shanghai, 200011, China.
  • 4 The First Affiliated Hospital, Department of Pulmonary Medicine, Chen, Wenzhou city, zhejiang Province, China.
  • 5 New Drug Research and Development Center, School of Pharmacy, Second Military Medical University, Shanghai, China.
  • 6 Institute of Life Sciences, Jiangsu University, Zhenjiang 212013, China.
PMID: 28266626 DOI: 10.1038/srep43940
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.

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