A recent study suggests that Agaricus extract has estrogen-like activity and may help prevent atherosclerosis via dual roles in cell signaling, macrophage development suppression and endothelial cell recovery from vascular damage (16). Both aqueous and organic extracts of Agaricus offered protection to cells exposed to methyl methanesulphonate, a mutagenic agent. The stimulus produced by linoleic acid on beta-DNA polymerase, an enzyme involved in repair mechanism following exposure of DNA to alkylating agents, is thought responsible for such an effect (19).
A major constituent of Agaricus, ergosterol, was found to inhibit tumor growth in mice via direct inhibition of tumor-induced angiogenesis (6). Other studies demonstrated that polysaccharides present in Agaricus extract caused activation of macrophages (5) or natural killer cells (17) and induced cytotoxic T-lymphocyte activity in tumor-bearing mice. Specifically, activation of natural killer cells was mediated through IL-12-induced IFN-gamma expression (18). Furthermore, Agaricus extract stimulates caspase 3 activation and reduces telomerase activity (19) possibly through regulation of Akt signaling (20) thereby inducing apoptosis in cancer cell lines. Blazeispirol A, produced by Agaricus fermentation, causes both caspase-dependent and -independent cell death in human Hep 3B cells (21). Agaritine, a hydrazine-containing constituent also exhibits anti-tumor activity toward U937 leukemic cells mediated through apoptosis (22).
In another study, polysaccharides isolated from Agaricus were shown to induce apoptosis in HL-60 cells through a signaling cascade of mitochondrial caspase-3-dependent pathway (28).