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

摘要

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-alpha (TNF-alpha), which acted as inducers of tumor cell apoptosis. Collectively, our findings suggest that APS can activate macrophages to release NO and TNF-alpha, 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.