Regulatory Functions of Tomato Lycopene in Cholesterol Metabolism: Implications in Atherosclerosis and Cancer

Alterations in cholesterol metabolism are implicated in atherosclerosis and cancer. Increased ingestion of tomatoes and tomato products, containing lycopene, has been associated with decreased risk of such chronic diseases, although the exact molecular mechanism is still unknown. We show new evidence that lycopene may exert its antiatherosclerotic and antitumoral effects through changes in mevalonate pathway and in cholesterol metabolism. In normal macrophages, lycopene dose-dependently reduced intracellular total cholesterol. Such an effect was associated with a decrease in cholesterol synthesis through a reduction of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase expression and with an increase in cholesterol efflux through an enhancement of ABCA1 and caveolin-1 expression. On the other hand, in prostatic, colon and lung cancer cells, the carotenoid inhibited tumor cell growth by a mechanism involving a reduction in HMG-CoA reductase expression and an inactivation of Ras, NF-kB and MAPK cascade. Lycopene and statins, applied together, reduced proinflammatory cytokine levels, suggesting that simultaneous administration of these substances could be a useful strategy for reducing inflammatory responses.