Effect of a glycoprotein from mushroom Hypsizygus marmoreus (Peck) Bigelow on growth and differentiation of human leukemic U937 cells

•HM-3A is able to inhibit the growth of U937 cells in the indirect model.•HM-3A is able to stimulate human mononuclear cells to secrete effective cytokines.•HM-3A is able to induce the differentiation and maturation of U937 cells.•HM-3A is able to be developed into an anti-leukemia ingredient in health food.

A non-lectin glycoprotein (HM-3A) isolated from the basidioma of edible mushroom Hypsizygus marmoreus (Peck) Bigelow was shown to be inhibitory against the growth of human myeloid leukemia U937 cells in our previous research. The present study further investigated the mechanisms of inhibition and differentiation in an indirect model. Human mononuclear cells (MNC) were stimulated by HM-3A for 1, 2 and 3 days to obtain the conditioned media (MNC-CM1, 2 and 3) that was effective in inhibiting the growth of U937 cells. The percentage of mature monocytes/macrophages among the cells and the total productivity of superoxide increased in the treatment and proved the differentiation-inducing effect of HM-3A-MNC-CM. The secretion of cytokines TNF-α, IL-2 and IFN-γ from the treated MNC were increased. Antibody neutralization tests of HM-3A-MNC-CM1 further showed that the growth inhibition effect of HM-3A can be attributed to the promotion in secretion of cytokines IFN-γ and TNF-α. We propose that HM-3A may stimulate human MNC to secrete cytokines IFN-γ and TNF-α to inhibit the growth of U937 cells, and that HM-3A may be developed into an anti-leukemia ingredient in health food.