White button mushrooms (Agaricus bisporous) are a potential breast cancer chemopreventive agent, as they suppress aromatase activity and estrogen biosynthesis. Therefore, we evaluated the activity of mushroom extracts in the estrogen receptor-positive/aromatase-positive MCF-7aro cell line in vitro and in vivo. Mushroom extract decreased testosterone-induced cell proliferation in MCF-7aro cells but had no effect on MCF-10A, a nontumorigenic cell line. Most potent mushroom chemicals are soluble in ethyl acetate. The major active compounds found in the ethyl acetate fraction are unsaturated fatty acids such as linoleic acid, linolenic acid, and conjugated linoleic acid. The interaction of linoleic acid and conjugated linoleic acid with aromatase mutants expressed in Chinese hamster ovary cells showed that these fatty acids inhibit aromatase with similar potency and that mutations at the active site regions affect its interaction with these two fatty acids. Whereas these results suggest that these two compounds bind to the active site of aromatase, the inhibition kinetic analysis indicates that they are noncompetitive inhibitors with respect to androstenedione. Because only conjugated linoleic acid was found to inhibit the testosterone-dependent proliferation of MCF-7aro cells, the physiologically relevant aromatase inhibitors in mushrooms are most likely conjugated linoleic acid and its derivatives. The in vivo action of mushroom chemicals was shown using nude mice injected with MCF-7aro cells. The studies showed that mushroom extract decreased both tumor cell proliferation and tumor weight with no effect on rate of apoptosis. Therefore, our studies illustrate the anticancer activity in vitro and in vivo of mushroom extract and its major fatty acid constituents.

Agaricus bisporus (white button mushroom) is one of the most popular culinary-medicinal mushrooms worldwide. This species has for decades been the subject of numerous scientific studies. The aim of this study was to examine the pro- or anti-inflammatory properties of A. bisporus and biomass extracts from in vitro cultures growing in Oddoux medium enriched withα-linolenic acid in colon epithelial Caco-2 cells activated with lipopolysaccharide (LPS) and tumor necrosis factor (TNF)-α. Incubation of Caco-2 cells with A. bisporus extracts resulted in decreased expression of cyclooxygenase-2 and prostaglandin F2α receptor compared with the LPS- and/or TNF-α-activated cells, whereas the expression of nuclear factor (erythroid-derived 2)-like 2 increased after incubation. Interleukin-6 level decreased significantly in Caco-2 cells after supplementation with mushroom extracts. The amounts of monoun-saturated and polyunsaturated fatty acids differed significantly in Caco-2 cell membranes after supplementation with A. bisporus extracts. Our findings suggest the presence of anti-inflammatory and antioxidant properties of A. bisporus biomass extracts from in vitro cultures.

The lectin from the common mushroom Agaricus bisporus, the most popular edible species in Western countries, has potent antiproliferative effects on human epithelial cancer cells, without any apparent cytotoxicity. This property confers to it an important therapeutic potential as an antineoplastic agent. The three-dimensional structure of the lectin was determined by x-ray diffraction. The protein is a tetramer with 222 symmetry, and each monomer presents a novel fold with two beta sheets connected by a helix-loop-helix motif. Selectivity was studied by examining the binding of four monosaccharides and seven disaccharides in two different crystal forms. The T-antigen disaccharide, Galbeta1-3GalNAc, mediator of the antiproliferative effects of the protein, binds at a shallow depression on the surface of the molecule. The binding of N-acetylgalactosamine overlaps with that moiety of the T antigen, but surprisingly, N-acetylglucosamine, which differs from N-acetylgalactosamine only in the configuration of epimeric hydroxyl 4, binds at a totally different site on the opposite side of the helix-loop-helix motif. The lectin thus has two distinct binding sites per monomer that recognize the different configuration of a single epimeric hydroxyl. The structure of the protein and its two carbohydrate-binding sites are described in detail in this study.

Analysis of vitamin B(12) in freshly harvested white button mushrooms ( Agaricus bisporus ) from five farms was performed by affinity chromatography and HPLC-ESI-MS techniques. The vitamin B(12) concentrations obtained varied from farm to farm, with higher concentrations of vitamin B(12) detected in outer peel than in cap, stalk, or flesh, suggesting that the vitamin B(12) is probably bacteria-derived. High concentrations of vitamin B(12) were also detected in the flush mushrooms including cups and flats. HPLC and mass spectrometry showed vitamin B(12) retention time and mass spectra identical to those of the standard vitamin B(12) and those of food products including beef, beef liver, salmon, egg, and milk but not of the pseudovitamin B(12), an inactive corrinoid in humans. The results suggest that the consumer may benefit from the consumption of mushroom to increase intake of this vitamin in the diet.

Estrogen is a major factor in the development of breast cancer. In situ estrogen production by aromatase/estrogen synthetase in breast cancer plays a dominant role in tumor proliferation. Because natural compounds such as flavones and isoflavones have been shown to be inhibitors of aromatase, it is thought that vegetables that contain these phytochemicals can inhibit aromatase activity and suppress breast cancer cell proliferation. Heat-stable extracts were prepared from vegetables and screened for their ability to inhibit aromatase activity in a human placental microsome assay. The white button mushroom (species Agaricus bisporus) suppressed aromatase activity dose dependently. Enzyme kinetics demonstrated mixed inhibition, suggesting the presence of multiple inhibitors or more than one inhibitory mechanism. "In cell" aromatase activity and cell proliferation were measured using MCF-7aro, an aromatase-transfected breast cancer cell line. Phytochemicals in the mushroom aqueous extract inhibited aromatase activity and proliferation of MCF-7aro cells. These results suggest that diets high in mushrooms may modulate the aromatase activity and function in chemoprevention in postmenopausal women by reducing the in situ production of estrogen.