Abstract

BackgroundBreast cancer is the most common cancer in women and affects 1.38 million women worldwide per year. Antiestrogens such as tamoxifen, a selective estrogen receptor (ER) modulator, are widely used in clinics to treat ER-positive breast tumors. However, remissions of breast cancer are often followed by resistance to tamoxifen and disease relapse. Despite the increasing understanding of the resistance mechanisms, effective regimens for treating tamoxifen-resistant breast cancer are limited. Antrodia cinnamomea is a traditional medicinal mushroom native only to Taiwan. In this study, we aimed to examine in vitro effect of antrodia cinnamomea in the tamoxifen-resistant cancer.MethodsAntrodia cinnamomea was studied for its biological activity against proliferation of tamoxifen-resistant breast cancer by XTT assay. Next, the underlying mechanism was studied by flow cytometry, qPCR and Western’s blotting assay.ResultsOur results revealed that the ethanol extract of antrodia cinnamomea (AC) can inhibit the growth of breast cancer cells, including MCF-7 cell and tamoxifen-resistant MCF-7 cell lines. Combination treatment with AC and 10− 6 M tamoxifen have the better inhibitory effect on the proliferation of tamoxifen-resistant MCF-7 cells than only AC did. AC can induce apoptosis in these breast cancer cells. Moreover, it can suppress the mRNA expression of skp2 (S-phase kinase-associated protein 2) by increasing the expressions of miR-21-5p, miR-26-5p, and miR-30-5p in MCF-7 and tamoxifen-resistant MCF-7 cells.ConclusionsThese results suggest that the ethanol extract of antrodia cinnamomea could be a novel anticancer agent in the armamentarium of tamoxifen-resistant breast cancer management. Moreover, we hope to identify additional pure compounds that could serve as promising anti-breast cancer candidates for further clinical trials.

Highlights

  • Breast cancer is the most common cancer in women and affects 1.38 million women worldwide per year

  • Effect of antrodia cinnamomea (AC) on the proliferation of different breast cancer cell lines To study the effects of AC on human estrogen receptor (ER)-positive breast cancer cells, MCF-7 cells and acquired tamoxifen-resistant MCF-7 cells were used as a tumor cell model

  • We tested the effects of various doses of AC on the proliferation of the two breast cancer cell lines through the XTT assay

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Summary

Introduction

Breast cancer is the most common cancer in women and affects 1.38 million women worldwide per year Antiestrogens such as tamoxifen, a selective estrogen receptor (ER) modulator, are widely used in clinics to treat ER-positive breast tumors. Remissions of breast cancer are often followed by resistance to tamoxifen and disease relapse. Breast cancer is the most common cancer in women and affects 1.38 million women worldwide per year [1]. In the past 20 years, the development of new therapeutics has significantly reduced mortality rates. Antiestrogens such as tamoxifen, a selective estrogen receptor modulator, are widely used in clinics to treat estrogen receptor (ER)-positive breast tumors. Remissions of breast cancer are often followed by resistance and disease relapse [3]. Developing treatment regimens for tamoxifen-resistant breast cancer that are more effective and accompanied by minimal adverse effects remains a priority in breast cancer research

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