Evaluation of the safety profiles of estrogenic Chinese herbal medicines in breast cancer

• Published in: Phytomedicine (Stuttgart) 2019-03, Vol.56, p.103-117
• Main Authors: Yue, Grace Gar-Lee, Wong, Lok-Sze, Leung, Hoi-Wing, Gao, Si, Tsang, Julia Yuen-Shan, Lin, Zhi-Xiu, Tse, Gary Man-Kit, Lau, Clara Bik-San
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents, Phytogenic - pharmacology; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Cistanche - chemistry; Cistanche deserticola; Dioscorea - chemistry; Dioscorea opposita; Drugs, Chinese Herbal - adverse effects; Drugs, Chinese Herbal - pharmacology; Estrogen receptor; Estrogenic herbs; Female; Humans; Mice, Inbred BALB C; Mice, SCID; Phytoestrogens - pharmacology; Safety; Xenograft Model Antitumor Assays
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2018.10.003

An increasing number of breast cancer patients in Asian countries has been found to consume dietary supplements including phytoestrogen-rich Chinese herbal medicines with an expectation to alleviate the side effects of conventional cancer therapies. The question of whether estrogenic Chinese herbal medicines are beneficial or detrimental to the health of breast cancer patients remains uncertain. The present study aimed at establishing a systematic approach to look at the safety profiles of estrogenic Chinese herbal medicines (CHM). The effects of estrogenic CHM on the growth of human breast cancer cells as well as the progression of breast tumors in mice have been investigated. Our results demonstrated that among 10 selected estrogenic CHM, the aqueous extracts of Cistanche deserticola (CD) and Dioscorea opposita (DO) at 0.4 to 1.6 mg/ml significantly stimulated cell viability in both estrogen receptor (ER)-positive (MDA-MB-361 and MCF-7) and ER-negative (SKBR3 and MDA-MB-231) breast cancer cells. However, results from animal studies showed that no significant difference was found on the size of mouse 4T1 breast tumors in CD- and DO-treated mice when compared with the control group, while the number of proliferative cells were found to be increased in DO-treated group. Besides, CD and DO treatments induced significant immunomodulatory effects on 4T1 tumor-bearing mice by increasing the production of cytokines IL-2 and IFN-γ and modulation of regulatory T-cells. Furthermore, CD and DO treatments did not stimulate, but in fact suppressed human triple-negative MDA-MB-231 breast xenografts growth in immunodeficiency mice. The considerable concerns on the use of CD and DO in breast cancer patients could be relieved to some extents upon the findings of this pre-clinical study. The potential harmful effects of estrogenic Chinese herbal medicines on breast cancer growth should be verified in both cell-based and tumor-bearing mice models. [Display omitted]