134
J. Pospíšil et al.
Indeed, it is probable that all previously mentioned plant phenolic compounds do not
interact with cellular targets as such. It is likely that after their absorption into the
bloodstream they are glycosylated, methylated, or glucuronidated. Accordingly, the
newly generated conjugates would then be responsible for the biological activities
observed [151, 152].
3.3.3 Biological Activities Related to Cancer, Inclusive of Inhibition
of Cellular Proliferation and Induction of Apoptosis
Angiogenesis is a fundamental process that is coordinated by various growth factors
and the cell adhesion of molecules (in endothelial and mural cells) that leads to premature degradation of extracellular matrixes, and to the migration and proliferation of
endothelial cells [153, 154]. Degradation of the extracellular matrix is mediated by
metalloproteinases that allows the generation of new and abundant blood vessels
[155, 156]. From the cancer viewpoint, angiogenesis plays an important part in
tumor mass generation, and therefore it is essential in tumor expansion. Not surprisingly, the United States Food and Drug Administration (FDA) has approved certain
angiogenesis inhibitors as a novel treatment option for cancer [157].
Recently, it was discovered that mixtures of phenols in red wine and green
tea prevent thrombin-induced activation of MMP2 in vascular smooth muscle
cells. Epigallocatechin-3-gallate (39) and epicatechin-3-gallate (46) (both green tea
phenolic esters, Fig. 9) can mimic a MMP-2-activation inhibitory effect [158, 159].
It was also discovered that these phenolic substances prevent Vascular Endothelial
Growth Factor (VEGF) expression. This major proangiogenic factor can stimulate
endothelial cell migration, proliferation, and the formation of new blood vessels. Red
wine phenols as well as anthocyanins such as delphinidin and cyanidin can prevent
VEGF expression and its release [160, 161].
The effects of dietary phenols on vascular endothelial and smooth muscle cells
(increase in vasodilatation, antiproliferative effects, antithrombotic factors, etc.)
suggest their antiatherogenic and vascular-protective role [154]. Such compounds
also exhibit a role in mediating the migration and proliferation of vascular cells.
In this context, resveratrol (31) (increasing the expression of the tumor suppressor
gene, protein p53), delphinidin (47) (through the cyclin D1 and A dependent pathways), and epigallocatechin-3-gallate (39) (induction of apoptosis), have shown some
effectiveness in this regard [161–163].
Interestingly, it was also demonstrated that the antioxidant activity of the abovementioned phenols is maintained even if they are administered orally. In such cases,
the naturally occurring forms of these compounds are possibly activated by bacterial
(intestines) and human (oral) enzymes [164]. Catechin (32) (present in tea) when
activated via this mechanism was shown to inhibit production of the metalloprotease
enzymes, inducing cell arrest and apoptosis [165–167]. Other mechanisms of action
concerning such activation have been shown by methoxylated flavonoids (present in
citrus fruits, pepper, and betel). The newly generated metabolites inhibit the formation of DNA adducts. These types of adducts are generally formed upon the influence
J. Pospíšil et al.
Indeed, it is probable that all previously mentioned plant phenolic compounds do not
interact with cellular targets as such. It is likely that after their absorption into the
bloodstream they are glycosylated, methylated, or glucuronidated. Accordingly, the
newly generated conjugates would then be responsible for the biological activities
observed [151, 152].
3.3.3 Biological Activities Related to Cancer, Inclusive of Inhibition
of Cellular Proliferation and Induction of Apoptosis
Angiogenesis is a fundamental process that is coordinated by various growth factors
and the cell adhesion of molecules (in endothelial and mural cells) that leads to premature degradation of extracellular matrixes, and to the migration and proliferation of
endothelial cells [153, 154]. Degradation of the extracellular matrix is mediated by
metalloproteinases that allows the generation of new and abundant blood vessels
[155, 156]. From the cancer viewpoint, angiogenesis plays an important part in
tumor mass generation, and therefore it is essential in tumor expansion. Not surprisingly, the United States Food and Drug Administration (FDA) has approved certain
angiogenesis inhibitors as a novel treatment option for cancer [157].
Recently, it was discovered that mixtures of phenols in red wine and green
tea prevent thrombin-induced activation of MMP2 in vascular smooth muscle
cells. Epigallocatechin-3-gallate (39) and epicatechin-3-gallate (46) (both green tea
phenolic esters, Fig. 9) can mimic a MMP-2-activation inhibitory effect [158, 159].
It was also discovered that these phenolic substances prevent Vascular Endothelial
Growth Factor (VEGF) expression. This major proangiogenic factor can stimulate
endothelial cell migration, proliferation, and the formation of new blood vessels. Red
wine phenols as well as anthocyanins such as delphinidin and cyanidin can prevent
VEGF expression and its release [160, 161].
The effects of dietary phenols on vascular endothelial and smooth muscle cells
(increase in vasodilatation, antiproliferative effects, antithrombotic factors, etc.)
suggest their antiatherogenic and vascular-protective role [154]. Such compounds
also exhibit a role in mediating the migration and proliferation of vascular cells.
In this context, resveratrol (31) (increasing the expression of the tumor suppressor
gene, protein p53), delphinidin (47) (through the cyclin D1 and A dependent pathways), and epigallocatechin-3-gallate (39) (induction of apoptosis), have shown some
effectiveness in this regard [161–163].
Interestingly, it was also demonstrated that the antioxidant activity of the abovementioned phenols is maintained even if they are administered orally. In such cases,
the naturally occurring forms of these compounds are possibly activated by bacterial
(intestines) and human (oral) enzymes [164]. Catechin (32) (present in tea) when
activated via this mechanism was shown to inhibit production of the metalloprotease
enzymes, inducing cell arrest and apoptosis [165–167]. Other mechanisms of action
concerning such activation have been shown by methoxylated flavonoids (present in
citrus fruits, pepper, and betel). The newly generated metabolites inhibit the formation of DNA adducts. These types of adducts are generally formed upon the influence