Genistein induces morphology change and G2/M cell cycle arrest by inducing p38 MAPK activation in macrophages

Genistein is a well known natural compound which is present in soy foods and exerts many beneficial functions such as anticancer, anti-inflammatory and antioxidant. However, until now little is known about the effects of genistein on the function of macrophages. The murine macrophage cell line RAW264.7 was used as target cell line. The results show that at concentrations of 50-100 μM, genistein reduced cell viability to 70%-80% (after 24 h) and 50%-60% (after 48 h), which was due to G2/M phase cell cycle arrest. Treatment of the macrophages with genistein for 24 or 48 h also led to significant morphological changes, such as elongation of the cells and development of long pseudopodia-like protrusions. By staining the F-actin cytoskeleton, we observed accumulation of actin-filaments at the edges of the cells. The morphology change and G2/M phase arrest after genistein treatment is due to the activation of the phosphorylation of MAP kinase p38. The morphology change and cell cycle arrest can be significantly reverted when treatment is combined with p38 inhibitor SB203580. Moreover, after treatment of the macrophages with genistein for 24 and 48 h, the phagocytotic efficiency for Candida albicans was decreased in a time- and dose-dependent manner which correlates to the morphology change. The production of cytokines (TNF-α) stimulated by C. albicans was strongly inhibited by genistein. In conclusion, genistein showed a strong immune modulatory effect on the macrophages.