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Pure Appl. Chem., 2002, Vol. 74, No. 8, pp. 1469-1477

Role of gene regulation in the anticancer activity of carotenoids

Yoav Sharoni*, Michael Danilenko, Shlomo Walfisch, Hadar Amir, Amit Nahum, Anat Ben-Dor, Keren Hirsch, Marina Khanin, Michael Steiner, Lilach Agemy, Gabriel Zango and Joseph Levy

Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University of the Negev and Soroka Medical Center of Kupat Holim, Beer-Sheva, Israel

Abstract: There is extensive evidence that high intake of fruits and vegetables is associated with decreased risk of many types of cancers. Thus, it is widely accepted that diet changes are a powerful means to prevent cancer. Although there is a growing interest in the role of the tomato carotenoid lycopene in cancer prevention and treatment, we hypothesize that a single micronutrient cannot replace the power of the concerted action of multiple agents derived from a diet rich in fruits and vegetables. Indeed, we found that lycopene can synergize with other phytonutrients in the inhibition of cancer cell growth. The mechanism underlying the inhibitory effects of lycopene and other carotenoids involves interference in several pathways related to cancer cell proliferation and includes changes in the expression of many proteins participating in these processes, such as connexins, cyclins, cyclin-dependent kinases, and their inhibitors. These changes in protein expression suggest that the initial effect involves modulation of transcription by ligand-activated nuclear receptors or by other transcription factors. It is feasible to suggest that carotenoids and their oxidized derivatives interact with a network of transcription systems that are activated by different ligands at low affinity and specificity and that this activation leads to the synergistic inhibition of cell growth.