title: Anti-aromatase activity of phytochemicals in white button mushrooms (Agaricus bisporus).
abstract: 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.
authors.affiliation: Department of Surgical Research, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA. schen@coh.org
authors.forename: Shiuan
authors.initials: S
authors.lastname: Chen
authors.forename: Sei-Ryang
authors.initials: SR
authors.lastname: Oh
authors.forename: Sheryl
authors.initials: S
authors.lastname: Phung
authors.forename: Gene
authors.initials: G
authors.lastname: Hur
authors.forename: Jing Jing
authors.initials: JJ
authors.lastname: Ye
authors.forename: Sum Ling
authors.initials: SL
authors.lastname: Kwok
authors.forename: Gayle E
authors.initials: GE
authors.lastname: Shrode
authors.forename: Martha
authors.initials: M
authors.lastname: Belury
authors.forename: Lynn S
authors.initials: LS
authors.lastname: Adams
authors.forename: Dudley
authors.initials: D
authors.lastname: Williams
mesh_terms: D000364:Agaricus; D000818:Animals; D016588:Anticarcinogenic Agents / Q000302:isolation & purification / Q000494:pharmacology; D001141:Aromatase / Q000378:metabolism; D047072:Aromatase Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000517:prevention & control*; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D005260:Female; D006801:Humans; D007700:Kinetics; D051379:Mice; D008819:Mice, Nude; D008517:Phytotherapy; D010920:Placenta / Q000187:drug effects / Q000502:physiology; D010936:Plant Extracts / Q000494:pharmacology*; D011247:Pregnancy; D014183:Transplantation, Heterologous
chemical_list: D016588:Anticarcinogenic Agents; D047072:Aromatase Inhibitors; D010936:Plant Extracts; D001141:Aromatase