Anti-tumor potential of astragalus polysaccharides on breast cancer cell line mediated by macrophage activation

• Published in: Materials Science & Engineering C 2019-05, Vol.98, p.685-695
• Main Authors: Li, Wenfang, Song, Kedong, Wang, Shuping, Zhang, Chenghong, Zhuang, Meiling, Wang, Yiwei, Liu, Tianqing
• Format: Article
• Language: English
• Subjects: Anticancer properties; Antitumor activity; Antitumor agents; Apoptosis; Astragalus membranaceus; Astragalus polysaccharides; Bcl-2 protein; Biomedical materials; Breast cancer; Cancer; Carbohydrates; Cell activation; Cell cycle; Cell growth; Cell proliferation; Chemotherapy; Gene expression; Gene regulation; Herbal medicine; Immune response; Immune system; Lymphocytes B; Macrophage activation; Macrophages; Materials science; Nitric oxide; Polysaccharides; Radiation therapy; Saccharides; TNF-α; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Tumors; Uronic acid
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2019.01.025

Adverse effects are pressing challenges produced by chemotherapy and radiotherapy for the treatment of breast cancer. Nontoxic herbal medicines are therefore considered as a favorable alternative. Astragalus membranaceus has attracted growing interest in the field of biomedicine thanks to its various biological activities, among which the anticancer activity is considered to be closely associated with its active component-astragalus polysaccharide (APS). Currently, direct anti-tumor activity and the activation of immune response of the host have been widely acknowledged as the mechanism by which APS exerts its anti-cancer activity. In this study, we aimed to investigate whether APS could inhibit the growth of MCF-7 cells and activate macrophages to further kill cancer cells. The results indicated that the obtained APS was a pyran-type polysaccharide, containing 89.75% total carbohydrate and a minor amount of uronic acid (9.3%). Although APS did not significantly inhibit the growth of MCF-7 cells growth, encouragingly, APS-activated RAW264.7 macrophages present anti-cancer activity as evidenced by (a) cell proliferation inhibition (with an inhibitory rate of 41%), (b) G1-phase cell cycle arrest, as well as (c) the regulation of apoptosis-related genes (Bax/Bcl-2, 13.26-fold increase than untreated cells). In addition, APS could upregulate the level of nitric oxide (NO) and tumor necrosis factor-α (TNF-α), which acted as inducers of tumor cell apoptosis. Collectively, our findings suggest that APS can activate macrophages to release NO and TNF-α, which directly blocks cancer cell growth. The anti-breast cancer effect of APS and the in vivo mechanism will be further elucidated with a review to provide a therapeutic strategy for breast cancer. •Astragalus polysaccharides (APS) failed to significantly retarded MCF-7 cells growth.•APS upregulated nitric oxide (NO) and tumor TNF-α production of activated RAW264.7 cells.•APS activated macrophages markedly induced MCF-7 apoptosis in a dose-dependent manner.•Increased expression of NO and TNF-α directly blocked MCF-7 cells growth.