Journal Article

Fractionation of high molecular weight tannins in grape seed extract and identification of procyanidin B2-3,3′-di-O-gallate as a major active constituent causing growth inhibition and apoptotic death of DU145 human prostate carcinoma cells

Chapla Agarwal, Ravikanth Veluri, Manjinder Kaur, Shen-Chieh Chou, John A. Thompson and Rajesh Agarwal

in Carcinogenesis

Volume 28, issue 7, pages 1478-1484
Published in print July 2007 | ISSN: 0143-3334
Published online February 2007 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgm045
Fractionation of high molecular weight tannins in grape seed extract and identification of procyanidin B2-3,3′-di-O-gallate as a major active constituent causing growth inhibition and apoptotic death of DU145 human prostate carcinoma cells

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Several studies have documented the anticancer and chemopreventive efficacy of grape seed extract (GSE) against various malignancies including prostate cancer (PCA). GSE is a complex mixture of polyphenols including gallic acid (GA), catechin (Cat), epicatechin (Epi) and procyanidins–oligomers of Cat and Epi, some of which are esterified with GA. Initial studies to identify the GSE components cytotoxic to human prostate carcinoma (DU145) cells demonstrated that GA and several crude chromatographic fractions containing procyanidin dimers and trimers were biologically active. The focus of the present work was to purify 14 procyanidins from the fractions and to identify those with highest activity toward growth inhibition, cell death and apoptosis in DU145 cells. The most active procyanidin was identified by mass spectrometry and enzymatic hydrolysis as the 3,3′-di-O-gallate ester of procyanidin dimer B2 (Epi–Epi). B2-digallate exhibited dose-dependent effects on DU145 cells over the range 25–100 μM, whereas GA exhibited comparable activity at lower doses but was highly lethal at 100 μM. Structure–activity studies demonstrated that all three hydroxyl groups of GA are necessary for activity, but a free carboxylic acid group is not required even though esterification reduced the activity of GA. These data, and the fact that non-esterified B2 exhibited little or no activity, suggest that the galloyl groups of B2-digallate are primarily responsible for its effects on DU145 cells. Taken together, these data identify procyanidin B2-3,3′-di-O-gallate as a novel biologically active agent in GSE that should be studied in greater detail to determine its effects against PCA.

Journal Article.  5090 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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