Inhibition of growth and cholesterol synthesis in breast cancer cells by oxidation products of β-carotene

Abstract

We have isolated and chemically characterized a polar oxidation product of β-carotene and tested the effect of a highly enriched fraction containing this compound on the growth and metabolism of breast cancer (MCF-7) cells. This fraction strongly inhibits cell growth and cholesterol synthesis in MCF-7 cells. Pretreatment of the cells with mevalonate overcomes inhibition of cell growth by the oxidized fraction. Addition of the antioxidant butylated hydroxytoluene protects against inhibition of the growth of MCF-7 cells by β-carotene but not by the oxidized fraction. Pretreatment of cells with mevalonate overcomes inhibition of cell growth by oxidation products of β-carotene but not by retinoic acid. The oxidized fraction neither stimulates activity nor inhibits binding of retinoic acid to its nuclear receptors (RXR-α, RXR-β, RXR-γ, RAR-α, RAR-β, RAR-γ, and peroxisome proliferation receptors) in transfection assays. Mevalonate does not protect retinoic acid-induced growth inhibition of MCF-7 cells. The major compound in the inhibitory fraction was identified by mass spectrometry and nuclear magnetic resonance spectroscopy as 5,8-endoperoxy-2,3-dihydro-β-apocarotene-13-one. Our data suggest that the β-carotene oxidation products we have isolated represent a class of compounds not previously described with potential antineoplastic activity.