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 17 β -estradiol (E 2 )-induced MCF-7 cell proliferation when E 2 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 ER β at a concentration of 1.00 × 10 − 6  M. The ER β -binding ability of hispolon was larger than ER α in the concentration range of 1.00 × 10 − 9  M and 1.00 × 10 − 7  M. Hispolon could increase the body weight coefficient, serum E 2 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-ER α and hispolon-ER β 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.