White button mushrooms as aromatase inhibitors

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http://www.biomedexperts.com/Abstract.bme/17178902/Anti-aromatase_activity_of_ph\

ytochemicals_in_white_button_mushrooms_Agaricus_bisporus

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.

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