INHIBITION OF GROWTH AND CHOLESTEROL-SYNTHESIS IN BREAST-CANCER CELLSBY OXIDATION-PRODUCTS OF BETA-CAROTENE

We have isolated and chemically characterized a polar oxidation produc t of beta-carotene and tested the effect of a highly enriched fraction containing this compound on the growth and metabolism of breast cance r (MCF-7) cells. This fraction strongly inhibits cell growth and chole sterol synthesis in MCF-7 cells. Pretreatment of the cells with mevalo nate overcomes inhibition of cell growth by the oxidized fraction. Add ition of the antioxidant butylated hydroxytoluene protects against inh ibition of the growth of MCF-7 cells by beta-caroteile but not by the oxidized fraction. Pretreatment of cells with mevalonate overcomes inh ibition of cell growth by oxidation products of beta-carotene bur not by retinoic acid. The oxidized fraction neither stimulates activity no r inhibits binding of retinoic acid to its nuclear receptors (RXR-alph a, RXR-beta, RXR-gamma, RAR-alpha, RAR-beta, RAI-gamma, and peroxisome proliferation receptors) in transfection assays. Mevalonate does not protect retinoic acid-induced growth inhibition of MCF-7 cells. The ma jor compound in the inhibitory fraction was identified by mass spectro metry and nuclear magnetic resonance spectroscopy as 5,8-endoperoxy-2, 3-dihydro-beta-apocarotene Our data suggest that the beta-carotene oxi dation products we have isolated represent a class of compounds not pr eviously described with potential antineoplastic activity. (C) Elsevie r Science Inc. 1998.