title: Anordrin Eliminates Tamoxifen Side Effects without Changing Its Antitumor Activity.
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.
authors.affiliation: 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.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Gu
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East-China University of Science, and Technology, 130 Meilong Road, Shanghai, 200237, China.
authors.forename: Wenping
authors.initials: W
authors.lastname: Xu
authors.affiliation: Obstetrics and Gynecology Hospital, Shanghai Ji Ai Genetics and IVF Institute, Institute of Reproduction and Development, Fudan University, Shanghai, 200011, China.
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Sun
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East-China University of Science, and Technology, 130 Meilong Road, Shanghai, 200237, China.
authors.forename: Bubing
authors.initials: B
authors.lastname: Zeng
authors.affiliation: 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.
authors.forename: Shuangjie
authors.initials: S
authors.lastname: Wang
authors.affiliation: The First Affiliated Hospital, Department of Pulmonary Medicine, Chen, Wenzhou city, zhejiang Province, China.
authors.forename: Nian
authors.initials: N
authors.lastname: Dong
authors.affiliation: 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.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The First Affiliated Hospital, Department of Pulmonary Medicine, Chen, Wenzhou city, zhejiang Province, China.
authors.forename: Chengshui
authors.initials: C
authors.lastname: Chen
authors.affiliation: New Drug Research and Development Center, School of Pharmacy, Second Military Medical University, Shanghai, China.
authors.forename: Long
authors.initials: L
authors.lastname: Yang
authors.affiliation: Obstetrics and Gynecology Hospital, Shanghai Ji Ai Genetics and IVF Institute, Institute of Reproduction and Development, Fudan University, Shanghai, 200011, China.
authors.forename: Guowu
authors.initials: G
authors.lastname: Chen
authors.affiliation: Obstetrics and Gynecology Hospital, Shanghai Ji Ai Genetics and IVF Institute, Institute of Reproduction and Development, Fudan University, Shanghai, 200011, China.
authors.forename: Aijie
authors.initials: A
authors.lastname: Xin
authors.affiliation: Institute of Life Sciences, Jiangsu University, Zhenjiang 212013, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Ni
authors.affiliation: 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.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D045744:Cell Line, Tumor; D003280:Contraceptives, Oral, Synthetic / Q000008:administration & dosage*; D016889:Endometrial Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D005260:Female; D064593:Heterografts; D006801:Humans; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D065626:Non-alcoholic Fatty Liver Disease / Q000139:chemically induced / Q000517:prevention & control*; D009635:Norandrostanes / Q000008:administration & dosage*; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D003280:Contraceptives, Oral, Synthetic; D009635:Norandrostanes; D013629:Tamoxifen; C010855:anordrin