[Frontiers in Bioscience S1, 258-274, June 1, 2009]

Carotenoids and lung cancer prevention

Sudipta Veeramachaneni1, Xiang-Dong Wang1

1Nutrition and Cancer Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Carotenoids and lung cancer risk
3.1. Evidence from epidemiological studies
3.2. Evidence from animal studies
3.2.1. Beta-carotene
3.2.2. Lycopene
3.2.3. Beta-cryptoxanthin
3.2.4. Alpha-carotene
4. Mechanisms of action of carotenoids against lung cancer
4.1. Carotenoid metabolites and the retinoid signaling pathway
4.2. Carotenoid metabolites and the mitogen-activated protein kinase (MAPK) pathway
4.3. Carotenoid metabolites and the insulin-like growth factor-1 (IGF-1) pathway
5. Summary
6. References

1. ABSTRACT

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.