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

Xiaoming Hu, Kevin M. White, Neil E. Jacobsen, David J. Mangelsdorf, Louise M. Canfield

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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. Copyright (C) 1998 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)567-574
Number of pages8
JournalJournal of Nutritional Biochemistry
Volume9
Issue number10
DOIs
StatePublished - Oct 1998

Keywords

  • Cancer
  • Cholesterol
  • MCF-7 cells
  • Mevalonate
  • Oxidation
  • β-carotene

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

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