Exp Cell Res. 2012 Aug 1;318(13):1586-96.
Diet-derived polyphenols inhibit angiogenesis by modulating the interleukin-6/STAT3 pathway.
Lamy S, Akla N, Ouanouki A, Lord-Dufour S, Béliveau R.
Source
Laboratoire de Médecine Moléculaire, Université du Québec à Montréal, C.P. 8888,
Succ. Centre-ville, Montréal, Québec, Canada H3C 3P8.
Abstract
Several epidemiological studies have indicated that abundant consumption of
foods from plant origin is associated with a reduced risk of developing several
types of cancers. This chemopreventive effect is related to the high content of
these foods in phytochemicals, such as polyphenols, that interfere with several
processes involved in cancer progression including tumor cell growth, survival
and angiogenesis. In addition to the low intake of plant-based foods, increased
body mass and physical inactivity have recently emerged as other important
lifestyle factors influencing cancer risk, leading to the generation of
low-grade chronic inflammatory conditions which are a key process involved in
tumor progression. The objectives of the current study are to investigate the
inhibitory effects of these polyphenols on angiogenesis triggered by an
inflammatory cytokine (IL-6) and to determine the mechanisms underlying this
action. We found that, among the tested polyphenols, apigenin and luteolin were
the most potent angiogenesis inhibitors through their inhibitory effect on the
inflammatory cytokine IL-6/STAT3 pathway. These effects resulted in modulation
of the activation of extracellular signal-regulated kinase-1/2 signaling
triggered by IL-6, as well as in a marked reduction in the proliferation,
migration and morphogenic differentiation of endothelial cells. Interestingly,
these polyphenols also modulated the expression of IL-6 signal transducing
receptor (IL-6R?) and the secretion of the extracellular matrix degrading enzyme
MMP-2 as well as the expression of suppressor of cytokine signaling (SOCS3)
protein. Overall, these results may provide important new information on the
role of diet in cancer prevention.
Copyright © 2012 Elsevier Inc. All rights reserved.
PMID: 22522122 [PubMed - indexed for MEDLINE]