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 iden-tify 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 TGF beta receptor in lung cancer cells. In parallel, ZnF3 activates macrophages via induction of TNF-alpha 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 demon-strates 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.

Automated summary

In this study, a 7.9 kDa Ac-SPS named ZnF3 was identified and found to have dual anti-cancer functions. It can inhibit cancer cells and activate macrophages. ZnF3 inhibits lung cancer cells by inducing subG1 population and apoptosis, and activates macrophages via induction of TNF-alpha and IL-6 secretion, NO production and phagocytosis.