Abstract
Preclinical and clinical studies have offered evidence for protective effects of various polyphenol-rich foods against cardiovascular diseases, neurodegenerative diseases, and cancers. Resveratrol is among the most widely studied polyphenols. However, the preventive and treatment effectiveness of resveratrol in cancer remain controversial because of certain limitations in existing studies. For example, studies of the activity of resveratrol against cancer cell lines in vitro have often been conducted at concentrations in the low μM to mM range, whereas dietary resveratrol or resveratrol-containing wine rarely achieve nM concentrations in the clinic. While the mechanisms underlying the failure of resveratrol to inhibit cancer growth in the intact organism are not fully understood, the interference by thyroid hormones with the anticancer activity of resveratrol have been well documented in both in vitro and xenograft studies. Thus, endogenous thyroid hormones may explain the failure of anticancer actions of resveratrol in intact animals, or in the clinic. In this review, mechanisms involved in resveratrol-induced antiproliferation and effects of thyroid hormones on these mechanisms are discussed.
Highlights
Clinical evaluation of resveratrol and other well-studied polyphenols as anticancer agents have at best yielded variable results [1,2,3,4,5,6,7,8,9,10]
Via specific binding to the cancer cell surface integrin, αvβ3, resveratrol sequentially induces the activation of ERK1/2, nuclear localization of sumoylated COX-2, phosphorylation of p53, and antiproliferation
The induction of antiproliferation by resveratrol depends upon the accumulation of resveratrol-induced nuclear COX-2, complexed with ERK1/2, and with p53, to form a complex with transcriptional activity
Summary
Clinical evaluation of resveratrol and other well-studied polyphenols as anticancer agents have at best yielded variable results [1,2,3,4,5,6,7,8,9,10]. Via specific binding to the cancer cell surface integrin, αvβ, resveratrol sequentially induces the activation of ERK1/2, nuclear localization of sumoylated COX-2, phosphorylation of p53, and antiproliferation. T4 and inhibits the appears formation ofkinases the intranuclear for pools of ERK1/2 between thyroid hormones resveratrol to divert pERK1/2-COX-2–p53 complex pathway, and consequent p53-dependent antiproliferation. Of pERK1/2–COX-2–p53 nuclear complexes in and resveratrol-exposed inhibits the expression of RRM2, which is caused by resveratrol Both tetrac and NDAT cells is not yet known. The activation of ERK1/2 induced by hormones and resveratrol is additive, the competition for pools of ERK1/2 between thyroid hormones and resveratrol appears to divert kinases to the cell proliferation pathway, and may play an important role in the inhibition by T4 of resveratrol's pro-apoptotic action.
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