Estrogenic Activity of Mycoestrogen (3β,5α,22E)-Ergost-22-en-3-ol via Estrogen Receptor α-Dependent Signaling Pathways in MCF-7 Cells.

Dahae Lee,You-Kyoung Choi,Changhyun Pang,Yuri Ko,Yoon-Joo Ko,Ki Sung Kang,Ki Hyun Kim

doi:10.3390/molecules27010036

Abstract

Armillariella tabescens (Scop.) Sing., a mushroom of the family Tricholomataceae, has been used in traditional oriental medicine to treat cholecystitis, improve bile secretion, and regulate bile-duct pressure. The present study evaluated the estrogen-like effects of A. tabescens using a cell-proliferation assay in an estrogen-receptor-positive breast cancer cell line (MCF-7). We found that the methanol extract of A. tabescens fruiting bodies promoted cell proliferation in MCF-7 cells. Using bioassay-guided fractionation of the methanol extract and chemical investigation, we isolated and identified four steroids and four fatty acids from the active fraction. All eight compounds were evaluated by E-screen assay for their estrogen-like effects in MCF-7 cells. Among the tested isolates, only (3β,5α,22E)-ergost-22-en-3-ol promoted cell proliferation in MCF-7 cells; this effect was mitigated by the ER antagonist, ICI 182,780. The mechanism underlying the estrogen-like effect of (3β,5α,22E)-ergost-22-en-3-ol was evaluated using Western blot analysis to detect the expression of extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K), Akt, and estrogen receptor α (ERα). We found that (3β,5α,22E)-ergost-22-en-3-ol induced an increase in phosphorylation of ERK, PI3K, Akt, and ERα. Together, these experimental results suggest that (3β,5α,22E)-ergost-22-en-3-ol is responsible for the estrogen-like effects of A. tabescens and may potentially aid control of estrogenic activity in menopause.

Highlights

Menopause, the complete end of menstrual periods, typically occurs worldwide for women 45 to 55 years of age
We examined MCF-7 cell proliferation after treatment with the MeOH extract of
Cell proliferation increased to 152.61 ± 4.73% after treatment, with 100 μg/mL of the MeOH extract compared with the untreated cells, and this effect was mitigated by ICI 182,780, an estrogen receptor (ER) antagonist (Figure 2A)

Summary

Introduction

The complete end of menstrual periods, typically occurs worldwide for women 45 to 55 years of age. The global number of menopausal women aged 50 years and over is estimated to reach 1.2 billion by 2030, with 47 million new entrants each year [1,2]. In South Korea, the postmenopausal female population aged over 50 years has increased since 2000. After 2030, over half of the female population will be postmenopausal (Figure 1), according to the Korean Statistical. Menopause results from declining ovarian function, and the production of steroid hormones such as estrogen dramatically drops. Menopause results in such vasomotor symptoms as hot flushes, night sweats, sleep disturbance, vaginal dryness, and even osteoporosis [4].

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