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.
** Corresponding author.
*Lecture presented at the 13 th International Symposium
on Carotenoids, Honolulu, Hawaii, USA, 6-11 January 2002.
Other lectures are published in this issue, pp. 1369-1477.
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