title: Estrogenic and anti-estrogenic activities of hispolon from Phellinus lonicerinus (Bond.) Bond. et sing.
abstract: Hispolon was the main antitumor active ingredient in Phellinus sensu lato species. In order to confirm the dual regulating estrogenic ingredient and obtain more effective natural estrogen replacement drugs, hispolon was separated from Phellinus lonicerinus (Bond.) Bond. et sing. Hispolon exhibited significant anti-proliferative effect against estrogen-sensitive ER (+) MCF-7 cells in the absence of estrogen, and exhibits antagonistic effects on 17β-estradiol (E2)-induced MCF-7 cell proliferation when E2 and the different concentrations of hispolon were treated simultaneously. Hispolon also inhibited the proliferation of estrogen-negative ER (-) MDA-MB-231 cells at the concentration of 5.00×10(-5) M. The yeast two-hybrid experiments showed that hispolon had strong and non-selective effects on the estrogen receptor (ER) α and ERβ at a concentration of 1.00×10(-6) M. The ERβ-binding ability of hispolon was larger than ERα in the concentration range of 1.00×10(-9) M and 1.00×10(-7) M. Hispolon could increase the body weight coefficient, serum E2 and progesterone contents in immature female mice at dose of 9.10×10(-6) mol/kg, and increase coefficient of thymus and spleen in mice. The Gscores of hispolon-ERα and hispolon-ERβ docked complexes were -7.93 kcal/mol and -7.79 kcal/mol in docking simulations. Hispolon presented dual regulating estrogenic activities, which showed estrogenic agonist activity at low concentration or lack of endogenous estrogen, and the estrogenic antagonistic effect was stimulated at high concentrations or too much endogenous estrogen. Hispolon could be used for treating the estrogen deficiency-related disease with the benefit of non-toxic to normal cells, good antitumor effects and estrogenic activity.
authors.affiliation: Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang 443002, China; Hubei Tujia Institute of Medicine, China Three Gorges University, Yichang 443002, China.
authors.forename: Junzhi
authors.initials: J
authors.lastname: Wang
authors.affiliation: Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang 443002, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Hu
authors.affiliation: Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang 443002, China.
authors.forename: Youcheng
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang 443002, China.
authors.forename: Huajun
authors.initials: H
authors.lastname: Luo
authors.affiliation: Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang 443002, China. Electronic address: hny115@126.com.
authors.forename: Nianyu
authors.initials: N
authors.lastname: Huang
authors.affiliation: Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang 443002, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Cheng
authors.affiliation: Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang 443002, China.
authors.forename: Zhangshuang
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
authors.forename: Weiqiao
authors.initials: W
authors.lastname: Deng
authors.affiliation: Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang 443002, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zou
mesh_terms: D000818:Animals; D001487:Basidiomycota / Q000737:chemistry*; D001835:Body Weight; D002396:Catechols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004965:Estrogen Antagonists / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000737:chemistry; D004967:Estrogens / Q000819:agonists* / Q000172:deficiency; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D013154:Spleen / Q000187:drug effects; D013950:Thymus Gland / Q000187:drug effects; D020798:Two-Hybrid System Techniques
chemical_list: D002396:Catechols; C506487:ESR1 protein, human; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D004967:Estrogens; C103442:hispolon
keywords: Breast cancer cells (MCF-7MDA-MB-231); Estrogenic and anti-estrogenic activity; Hispolon; Phellinus lonicerinus (Bond.) Bond. et sing; Yeast two-hybrid assay