Carotenoids and lung cancer prevention.

Understanding the molecular actions of carotenoids is critical for human studies involving carotenoids for prevention of lung cancer and cancers at other tissue sites. While the original hypothesis prompting the beta carotene intervention trials was that beta carotene exerts beneficial effects through antioxidant activity, the harmful effects of beta carotene led to further animal and cell culture studies showing that the free radical rich but antioxidant poor environment of smoker's lungs could decrease the stability of the beta carotene molecule and increase beta carotene oxidative metabolites or decomposition products. In addition, the beneficial vs. detrimental effects of carotenoids are related to the carotenoid dose administered in vivo, and the tissue accumulation of carotenoids and their metabolites. This review will discuss the recent understanding that the biological functions of carotenoids are mediated via their oxidative metabolites through their effects on several important cellular signaling pathways and molecular targets, as well as smoke-related lung cancer.