Carotenoids and modulation of cancer: molecular targets

Epidemiological studies have suggested an association between an increased dietary intake of carotenoids and a reduced incidence of cancer, even if results from clinical trials indicated that �-carotene supplements do not protect against cancer and might actually increase the risk of lung cancer in smokers. Although several mechanisms by which carotenoids modulate cancer process have been reported, there are still conflicting opinions and little is known regarding their mechanisms of action at molecular levels. It appears that carotenoids can bring about a host of changes at the levels of both gene expression and protein activity in the cells. In particular, some evidences are shown that carotenoid molecules may interfere in cancer related molecular pathways and change the expression of many proteins involved in: 1) cell proliferation, differentiation, apoptosis and angiogenesis; 2) carcinogen detoxification; 3) DNA damage and repair; 4) immunosurveillance. Carotenoids seem to affect gene expression either directly by interference with the control apparatus of the gene expression machinery or by virtue of metabolites or metabolic conditions induced (hormonal status, cellular redox status, etc.) that, in turn, alter cell functions implicated in the cancer process. The suppression as well as the induction of cancer by carotenoids raises issues about possible doses of carotenoid administration, possible synergy as well as antagonistic interactions between carotenoids and other dietary components. Understanding the effects of carotenoids on cancer-related genetic pathways is fundamental, not only providing pathophysiological explanation for the development of cancer, but also improving strategies for cancer prevention.