ZnF3, a sulfated polysaccharide from Antrodia cinnamomea, inhibits lung cancer cells via induction of apoptosis and activation of M1-like macrophage-induced cell death

Sulfated polysaccharides (Ac-SPSs) of Antrodia cinnamomea present anti-cancer activity. However, the anti-cancer mechanism of Ac-SPSs is not fully understood and remains largely unexplored. In this study, we identify an Ac-SPS with 7.9 kDa, noted ZnF3, and aim to examine the dual anti-cancer functio...

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Bibliographic Details
Published in:International journal of biological macromolecules 2023-05, Vol.238, p.124144-124144, Article 124144
Main Authors: Lin, Zhi-Hu, Lu, Mei-Kuang, Lo, Hung-Chih, Chang, Chia-Chuan, Tseng, Ai-Jung, Chao, Chi-Hsein, Lin, Tung-Yi
Format: Article
Language:English
Subjects:
Anti-cancer activity
Antrodia
Antrodia cinnamomea
Apoptosis
Cell Death
Humans
Lung Neoplasms - drug therapy
Macrophage
Macrophages
Polysaccharides - pharmacology
Sulfated polysaccharides
Sulfates - pharmacology
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Summary:Sulfated polysaccharides (Ac-SPSs) of Antrodia cinnamomea present anti-cancer activity. However, the anti-cancer mechanism of Ac-SPSs is not fully understood and remains largely unexplored. In this study, we identify an Ac-SPS with 7.9 kDa, noted ZnF3, and aim to examine the dual anti-cancer functions of ZnF3 on inhibiting cancer cells and activating macrophages. A biological study shows that ZnF3 inhibits lung cancer cells by inducing subG1 population and apoptosis. ZnF3 downregulates the expression of TGFβ receptor in lung cancer cells. In parallel, ZnF3 activates macrophages via induction of TNF-α and IL-6 secretion, NO production and phagocytosis. ZnF3 activates AKT/mTOR pathway and induces M1 type macrophage polarization. Cancer cells co-cultured with ZnF3-stimulated macrophages, leading to inhibition of lung cancer cells. This study demonstrates that ZnF3 not only directly inhibits cancer cells but also activates macrophages-mediated cytotoxic effect on cancer cells. Moreover, ZnF3 may be a supplement for suppressing lung cancer cells. •ZnF3 is a glucose-rich sulfated polysaccharides with 7.9 kDa.•ZnF3 exhibits anti-cancer activity.•ZnF3 induces apoptosis in lung cancer cells.•ZnF3 enhances M1 type macrophage polarization via ATK/mTOR pathway.•ZnF3-stimulated macrophages inhibit cancer cells.
ISSN:0141-8130
1879-0003
DOI:10.1016/j.ijbiomac.2023.124144