Angelica sinensis induces human hormone-sensitive breast cancer growth via ER[alpha]-mediated signaling pathway

Abstract

Breast cancer is one of the most common malignancies in women worldwide. Chemotherapy and endocrine therapy are major treatments for estrogen receptor (ER)-positive breast cancer, which might accompany with possible side effects including hot flashes, menstrual irregularity and other premature menopause symptoms. Angelica sinensis is traditionally used for relieving gynecological discomforts, and it is also popularly used for cancer therapeutics among breast cancer patients. However, study on the safe use of Angelica sinensis on women with breast cancer is insufficient.

This study was designed to investigate both in vitro and in vivo effects of aqueous Angelica sinensis extract on the MCF-7 (ER-positive) and MDAMB-231 (ER-negative) breast cancer cell lines. The effect of Angelica sinensis extract on cell viability was tested using MTS assay, and in vivo effect was evaluated using subcutaneous xenograft tumor mouse model. It was observed that Angelica sinensis extract promoted the cell proliferation of MCF-7, and the tumor size of extract treatment group was significantly larger than the control group in MCF-7 xenografts. However, in MDAMB-231 cell line, Angelica sinensis extract showed little influence on the growth of either cells or tumor sizes. Due to the different actions between ER-positive and ER-negative cell lines, ER alpha was considered to play a critical role in this extract-induced cancer growth. Western blot analysis indicated that Angelica sinensis extract could increase the ER alpha protein level both in cell lysates and tumor tissues. Furthermore, Tamoxifen, a representative ER antagonist in breast tissue, could suppress the Angelica sinensis extract-induced hormone-sensitive breast cancer growth in vivo.

Overall, this study suggests that Angelica sinensis extract can promote the growth of ER-positive breast cancer partially through ER-mediated signaling pathway, which may raise safety concerns of using Angelica sinensis for hormone-sensitive breast cancer patients.