Carotenoids as Modulators of Intracellular Signaling Pathways

Carotenoids have been proposed to exert beneficial effects in several chronic diseases, including cancer and cardiovascular diseases. Many of the biological actions of carotenoids have been attributed to their antioxidant properties, through the antioxidant capacity of the carotenoid molecule per se or through their possible influences on intracellular redox status. However, the exact mechanism by which carotenoids exert their beneficial effects are still under debate. Increasing evidence show that carotenoids, and their metabolites, may modulate molecular pathways involved in cell proliferation, acting at Akt, tyrosine kinases, mitogen activated protein kinase (MAP kinase) and growth factor signalling cascades. Moreover, there is now strong evidence for an involvement of carotenoids in the regulation of apoptosis through modulatory effects on the activation of caspase cascade and on the expression of Bcl-2 family proteins and transcription factors. Inhibitory or stimulatory actions at these pathways are likely to affect cellular functions by altering the phosphorylation state of target molecules and by modulating gene expression. A clear understanding of the mechanisms of action of carotenoids, either as redox agents or modulators of cell signalling and the influence of their metabolism on these properties is key to the evaluation of these biomolecules as anticancer and cardioprotective agents.