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  • Astragalus polysaccharides br Macrophage activation

    2022-05-22

    Astragalus polysaccharides
    Macrophage activation
    Breast cancer
    Apoptosis TNF-α 
    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 in-vestigate 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 PFTα (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.
    1. Introduction
    Breast cancer is the most common cancer and the second leading cause of cancer-related death among women following lung cancer [1]. Although considerable progress against cancer has been achieved, multi-faceted challenges still remain including the severe adverse ef-fects caused by chemotherapy and radiotherapy and the drug resistance developed over time [2]. Therefore, more attentions have been paid on new anti-cancer strategies, such as herbal medicines or natural products which are considered nontoxic, multi-targeted and do not lead to the development of drug resistance.
    Currently, polysaccharides have attracted considerable attention in biomedical field due to their various pharmacological activities [3,4]. Among the polysaccharides identified, astragalus polysaccharide (APS), the primary active component extracted from Chinese medicinal herb
    Astragalus membranaceus, has been shown to exhibit broad-range in-hibitory effect on various types of solid tumors [5]. Previous report demonstrated APS exhibited favorable anti-melanoma potency by down-regulating CD40 expression [6]. Besides, APS exerted a sy-nergistic anti-tumor effect in combination with other chemotherapy agents with increased sensitivity and decreased side-effects. Tian et al. reported that APS combined with adriamycin yielded an enhanced anti-tumor activity in H22 tumor-bearing mice by regulating immune cy-tokines [7]. Despite these progresses, the anti-tumorigenic activity and mechanism of APS against breast carcinogenesis has rarely been re-ported.
    The anti-tumor activity of polysaccharides is generally mediated via two major pathways: direct inhibitory/eradicative effect against ma-lignant cells, and activated innate and/or adaptive immune system, while the latter contributes to the activation of various immune cells
    Corresponding author at: State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, 116024, China.