Use of Grape Polyphenols Against Carcinogenesis: Putative Molecular Mechanisms of Action Using In Vitro and In Vivo Test Systems

Abstract

Polyphenols are present in foods and beverages and are related to sensorial qualities such as color, bitterness, and astringency, which are relevant in wine, tea, grape juice, and other products. These compounds occur naturally in forms varying from simple phenolic acids to complex polymerized tannins. Thus, it is reasonable to expect that grape-derived products elaborated in the presence of skins and seeds, such as wine and grape juice, are natural sources of flavonoids in the diet. Carcinogenesis is a multistep process that is characterized by genetic, epigenetic, and phenotypic changes. With increasing knowledge of these mechanisms, and the conclusion that most cases of cancer are preventable, efforts have focused on identifying the agents with potential anticancer properties. The use of grape polyphenols against the carcinogenesis process seems to be a suitable alternative for either prevention and/or therapeutic purposes. The aim of this article is to show the molecular data generated from the use of grape polyphenols against carcinogenesis using in vivo and in vitro test systems.

Proanthocyanidins and hydrolysable tannins: occurrence, dietary intake and pharmacological effects

“…Proanthocyanidins have been extensively studied on a wide range of cancer cells. GSPs induced p53‐dependent apoptosis on JB6 C141 mouse skin epidermal cells, through involvement of Bax/Bcl‐2 proteins and caspase‐3 activation (Gollucke et al, ). Furthermore, inhibition of the phosphorylation of proteins belonging to the MAPK family and activation of NF‐κB and its related genes were observed in normal human epidermal keratinocytes (Gollucke et al, ).…”

“…GSPs induced p53‐dependent apoptosis on JB6 C141 mouse skin epidermal cells, through involvement of Bax/Bcl‐2 proteins and caspase‐3 activation (Gollucke et al, ). Furthermore, inhibition of the phosphorylation of proteins belonging to the MAPK family and activation of NF‐κB and its related genes were observed in normal human epidermal keratinocytes (Gollucke et al, ). The same molecular mechanisms were found to be involved in the inhibition of cell growth and in the down‐regulation of MMP‐2 and ‐9 in both androgen‐insensitive (DU145) and in androgen‐sensitive human prostate carcinoma cells (LNCaP) (Gollucke et al, ) on which GSPs also seem able to regulate androgen receptor‐mediated transcription through potent anti‐histone acetyltransferase activity (Park et al, ).…”

“…Furthermore, inhibition of the phosphorylation of proteins belonging to the MAPK family and activation of NF‐κB and its related genes were observed in normal human epidermal keratinocytes (Gollucke et al, ). The same molecular mechanisms were found to be involved in the inhibition of cell growth and in the down‐regulation of MMP‐2 and ‐9 in both androgen‐insensitive (DU145) and in androgen‐sensitive human prostate carcinoma cells (LNCaP) (Gollucke et al, ) on which GSPs also seem able to regulate androgen receptor‐mediated transcription through potent anti‐histone acetyltransferase activity (Park et al, ). The down‐regulation of these MMPs , involved in tumour development and metastasis, was also observed in pancreatic carcinoma cells (Chung et al, ).…”

“…GSPs interfered with normal regulation of cell‐cycle progression inducing an up‐regulation of Cip1/p21 and Kip1/p27 protein levels together with a down‐regulation of cyclins (D1, D2 and E) and cyclin‐dependent kinases (CDK2, CDK4 and CDK6) leading to Go/G1 phase arrest (Prasad and Katiyar, ). Concentration‐dependent effects of GSPs were observed on breast and lung cancer and gastric adenocarcinoma cells (Gollucke et al, ).…”

Therapeutic Potential of Polyphenols from Epilobium Angustifolium (Fireweed)

“…Polyphenols are mainly natural but can also be synthetic or semisynthetic. Plant-derived polyphenols exhibit beneficial effects on human health because of their antiinflammatory, anti-allergic, anti-atherogenic, antimicrobial, anti-viral, anti-proliferative, and immunomodulatory properties (Feldman, 2005;Okuda, 2005;Holderness et al, 2008;Stagos et al, 2012;Gollucke et al, 2013;Korkina et al, 2013;Chirumbolo, 2014;Ratz-Lyko et al, 2015). The ability of natural polyphenols to modulate certain immune responses may explain, in part, some of beneficial effects of various medicinal plants.…”