phytoestrogens and hispolon

We studied Phellinus lonicerinus to determine the cytotoxic effect and the dual estrogenic activities of methyl-hispolon and their relation to estrogen signals in vivo and in vitro. The Glide scores of methyl-hispolon-estrogen receptor α (ERα) and methyl-hispolon-ERβ docked complexes were -7.29 kcal/mol and -6.68 kcal/mol in docking simulations. Methyl-hispolon had a significant antiproliferative effect for estrogen-sensitive ER(+) MCF-7 cells in the absence of estrogen, and it exhibited dual estrogen activities. Methyl-hispolon increased the serum E2 in rats with premature ovarian failure and fulfilled the estrogenic function in the uterus and ovary. Methyl-hispolon significantly inhibited the expression of Ras, API, ERα, C-myc, and cyclinDl, as well as their gene transcription in RL95-2 cells. The phosphorylation of ERK1/2 was inhibited by methyl-hispolon. Thus, methyl-hispolon has potential use in treating estrogen deficiency-related diseases, with good antitumor effects and estrogenic activity.

Topics: Aging, Premature; Animals; Basidiomycota; Catechols; Cell Proliferation; Estrogen Receptor alpha; Estrogen Receptor beta; Estrogen Receptor Modulators; Estrogens; Female; Hormone Replacement Therapy; Humans; MAP Kinase Signaling System; MCF-7 Cells; Molecular Docking Simulation; Ovary; Phosphorylation; Phytoestrogens; Rats; Rats, Sprague-Dawley; Uterus

Phytoestrogen has previously been proposed as an alternative to hormone replacement therapy. Hispolon has been found to have phytoestrogenic properties. However, the possible effects of hispolon on estrogen receptors and other related molecules remain to be determined. This study was performed mainly to confirm the estrogenic function of hispolon as it relates to estrogen receptors, aromatase, and cyclooxygenase 2 (COX-2). Hispolon was shown to increase the serum 17β-estradiol in vivo. Immunohistochemical staining methods showed that hispolon exhibited a biphasic effect on ERα/β and aromatase expression in MCF-7 cells. Hispolon could also significantly inhibit aromatase activity, assessed using the enzyme-linked immunosorbent assay. Western blotting showed that COX-2 and aromatase could be inhibited by hispolon. These results further prove the phytoestrogenic features of hispolon and explore some pharmacological mechanisms that suggest that hispolon could be useful in the treatment of breast cancers or other gynecologic diseases.

Topics: Antineoplastic Agents; Aromatase; Basidiomycota; Blotting, Western; Catechols; Cyclooxygenase 2; Enzyme Inhibitors; Enzyme-Linked Immunosorbent Assay; Humans; MCF-7 Cells; Phytoestrogens; Receptors, Estrogen