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Biochemical and Molecular Actions of Nutrients

Carotenoids Normally Present in Serum Inhibit Proliferation and Induce Differentiation of a Human Monocyte/Macrophage Cell Line (U937)¹

University of the Sciences in Philadelphia, Department of Pharmaceutical Sciences, Philadelphia, PA and ^* U.S. Department of Agriculture Human Nutrition Research Center, Beltsville, MD

²To whom correspondence should be addressed. E-mail: d.morel{at}usip.edu.

Carotenoids, plant pigments with potent antioxidant activity, are implicated in chronic disease protection. They are absorbed from the diet and transported by plasma lipoproteins. Monocytes, as circulating blood cells, are exposed to carotenoid-rich lipoproteins. Such exposure may lead to enrichment with carotenoids and may affect the functions of monocyte-derived macrophages. This study explored the effect of cellular enrichment in vitro with ß-carotene, lycopene, or lutein on monocyte/macrophage function, using U937 cells as a model. Cell proliferation, production of reactive oxygen species, and cell-substrate adhesion were examined. Maximal carotenoid levels in medium supplemented with preenriched human serum were 2–8 µmol/L; incubation for 1–6 d resulted in 0.2–1.1 nmol carotenoid/mg cell protein (0.25–1 nmol/10⁶ cells), 10-fold more than that reported in normal tissue in vivo but within the range that might be anticipated with dietary supplementation. ß-Carotene, lycopene, and lutein markedly inhibited the proliferation of U937 cells, to an extent similar to or greater than that due to phorbol myristic acetate, a known differentiation/activation agent. Lycopene, but not ß-carotene or lutein, caused a significant increase in reactive oxygen species, indicating the induction of cell differentiation. Adhesion and LDL oxidation were unaffected. Thus, cellular carotenoids inhibit proliferation, and for lycopene at least, this may involve cell differentiation. The effectiveness of lycopene, a nonprovitamin A carotenoid, is consistent with a vitamin A–independent pathway modulating cell function.

KEY WORDS: • human • carotenoids • monocytes/macrophages • U937 cells • differentiation

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