Research article summary (published 30 Aug 1999):

Anti-tumor-promoting activity of a polyphenolic fraction isolated from grape seeds in the mouse skin two-stage initiation-promotion protocol and identification of procyanidin B5-3'-gallate as the most effective antioxidant constituent.

Full Abstract

Procyanidins present in grape seeds are known to exert anti-inflammatory, anti-arthritic and anti-allergic activities, prevent skin aging, scavenge oxygen free radicals and inhibit UV radiation-induced peroxidation activity. Since most of these events are associated with the tumor promotion stage of carcinogenesis, these studies suggest that grape seed polyphenols and the procyanidins present therein could be anticarcinogenic and/or anti-tumor-promoting agents. Therefore, we assessed the anti-tumor-promoting effect of a polyphenolic fraction isolated from grape seeds (GSP) employing the 7,12-dimethylbenz[a]anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol 13-acetate (TPA)-promoted SENCAR mouse skin two-stage carcinogenesis protocol as a model system. Following tumor initiation with DMBA, topical application of GSP at doses of 0.5 and 1.5 mg/mouse/application to the dorsal initiated mouse skin resulted in a highly significant inhibition of TPA tumor promotion. The observed anti-tumor-promoting effects of GSP were dose dependent and were evident in terms of a reduction in tumor incidence (35 and 60% inhibition), tumor multiplicity (61 and 83% inhibition) and tumor volume (67 and 87% inhibition) at both 0.5 and 1.5 mg GSP, respectively. Based on these results, we directed our efforts to separate and identify the individual polyphenols present in GSP and assess their antioxidant activity in terms of inhibition of epidermal lipid peroxidation. Employing HPLC followed by comparison with authentic standards for retention times in HPLC profiles, physiochemical properties and spectral analysis, nine individual polyphenols were identified as catechin, epicatechin, procyanidins B1-B5 and C1 and procyanidin B5-3'-gallate. Five of these individual polyphenols with evident structural differences, namely catechin, procyanidin B2, procyanidin B5, procyanidin C1 and procyanidin B5-3'-gallate, were assessed for antioxidant activity. All of them significantly inhibited epidermal lipid peroxidation, albeit to different levels. A structure-activity relationship study showed that with an increase in the degree of polymerization in polyphenol structure, the inhibitory potential towards lipid peroxidation increased. In addition, the position of linkage between inter-flavan units also influences lipid peroxidation activity; procyanidin isomers with a 4-6 linkage showed stronger inhibitory activity than isomers with a 4-8 linkage. A sharp increase in the inhibition of epidermal lipid peroxidation was also evident when a gallate group was linked at the 3'-hydroxy position of a procyanidin dimer. Procyanidin B5-3'-gallate showed the most potent antioxidant activity with an IC(50) of 20 microM in an epidermal lipid peroxidation assay. Taken together, for the first time these results show that grape seed polyphenols possess high anti-tumor-promoting activity due to the strong antioxidant effect of procyanidins present therein. In summary, grape seed polyphenols in general, and procyanidin B5-3'-gallate in particular, should be studied in more detail to be developed as cancer chemopreventive and/or anticarcinogenic agents.

Author information

Author/s: Zhao, J (J); Wang, J (J); Chen, Y (Y); Agarwal, R (R);

Affiliation: Center for Cancer Causation and Prevention, AMC Cancer Research Center, Denver, CO 80214, USA.

Grants: CA64514 (Agency:NCI NIH HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.

Journal: Carcinogenesis (Carcinogenesis), published in ENGLAND. (Language: eng)

Reference: 1999-Sep; vol 20 (issue 9) : pp 1737-45

Dates: Created 1999/09/30; Completed 1999/09/30; Revised 2007/11/14;

PMID: 10469619, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

9,10-Dimethyl-1,2-benzanthracene Acetone Administration, Cutaneous Animals Anticarcinogenic Agents - isolation & purification; pharmacology; therapeutic use Antioxidants - isolation & purification; pharmacology; therapeutic use Ascorbic Acid - pharmacology Biflavonoids Catechin - isolation & purification; pharmacology; therapeutic use Cocarcinogenesis Epidermis - drug effects Female Flavonoids Lipid Peroxidation - drug effects

Lipid Peroxidation - drug effects Mice Mice, Inbred SENCAR Microsomes - metabolism Molecular Structure Phenols - isolation & purification; pharmacology; therapeutic use Plant Extracts - chemistry Polymers - isolation & purification; pharmacology; therapeutic use Proanthocyanidins Rosales Seeds - chemistry Skin Neoplasms - chemically induced; prevention & control Tetradecanoylphorbol Acetate Vitamin E - pharmacology

Associated Chemicals: Anticarcinogenic Agents (0) ; Antioxidants (0) ; Biflavonoids (0) ; Flavonoids (0) ; Phenols (0) ; Plant Extracts (0) ; Polymers (0) ; Proanthocyanidins (0) ; procyanidin B5 (0) ; procyanidin B5 3'-O-gallate (0) ; procyanidin B5-3'-gallate (0) ; Vitamin E (1406-18-4) ; Catechin (154-23-4) ; Tetradecanoylphorbol Acetate (16561-29-8) ; procyanidin B2 (29106-49-8) ; Ascorbic Acid (50-81-7) ; 9,10-Dimethyl-1,2-benzanthracene (57-97-6) ; Acetone (67-64-1)

Related articles

These are the highest related articles currently in the database:

• Comparative antioxidant and cytotoxic effect of procyanidin fractions from grape and pine. 6 Sep 2007
• Assessment of the polyphenolic composition of the organic extracts of Mauritian black teas: a potential contributor to their antioxidant functions. 30 Dec 2005
• Inhibition of TPA-induced tumor promotion in CD-1 mouse epidermis by a polyphenolic fraction from grape seeds. 27 Jan 1999
• Comparative study of eight well-known polyphenolic antioxidants. 30 Aug 2003
• Cancer prevention by tea polyphenols is linked to their direct inhibition of antiapoptotic Bcl-2-family proteins. 29 Nov 2003
• Aqueous extract of peanut skin and its main constituent procyanidin A1 suppress serum IgE and IgG1 levels in mice-immunized with ovalbumin. 29 Apr 2007
• Effects of cacao liquor proanthocyanidins on PhIP-induced mutagenesis in vitro, and in vivo mammary and pancreatic tumorigenesis in female Sprague-Dawley rats. 26 Nov 2002
• Proanthocyanidin glycosides and related polyphenols from cacao liquor and their antioxidant effects. 30 Mar 2002
• Valorization of grape (Vitis vinifera) byproducts. Antioxidant and biological properties of polyphenolic fractions differing in procyanidin composition and flavonol content. 16 Dec 2002

See 100+ related articles.

Related Article Map

Legend: - FREE Full text Article. - Abstract only. - Title only. More help.

See a large map of 100+ related articles.