PURPOSE: Present study assessed the influence of gallate esterification on the anti-cancer activity of procyanidin B2 (B2) in androgen-dependent human prostate carcinoma LNCaP cells employing B2-3,3'-di-O-gallate (B2-G(2)), two mono-gallate esters B2-3-O-gallate (B2-3G) and B2-3'-O-gallate (B2-3'G) and the parent compound B2, all isolated from grape seed extract (GSE). MATERIALS AND METHODS: Study compounds were isolated from GSE by several chromatographic steps and structures determined by a combination of enzymatic hydrolysis, mass spectrometry and comparisons with standards. Cells, treated with these compounds, were assessed for viability and apoptosis and examined by western blotting. RESULTS: Gallate esters B2-G(2), B2-3G and B2-3'G significantly decreased LNCaP cell viability; however, B2 and gallic acid were ineffective. Furthermore, only B2-G(2) also significantly decreased cell growth. Decreases in cell viability were largely due to apoptosis induction with B2-G(2) and B2-3'G exhibiting comparable effects, whereas B2-3G was less effective. In mechanistic studies, B2-G(2) and B2-3'G treatments caused caspases-9 and -3 and PARP cleavage, and down-regulated Bcl-2, Bcl-Xl and androgen receptor levels. CONCLUSION: Together, our findings demonstrate anti-PCA efficacy of B2-G(2) and suggest that a gallate ester moiety at 3' position of procyanidin B2 contributes more extensively toward the biological activity of the di-gallate ester than esterification of position 3.
PURPOSE: Present study assessed the influence of gallate esterification on the anti-cancer activity of procyanidin B2 (B2) in androgen-dependent human prostate carcinomaLNCaP cells employing B2-3,3'-di-O-gallate (B2-G(2)), two mono-gallate estersB2-3-O-gallate (B2-3G) and B2-3'-O-gallate (B2-3'G) and the parent compound B2, all isolated from grape seed extract (GSE). MATERIALS AND METHODS: Study compounds were isolated from GSE by several chromatographic steps and structures determined by a combination of enzymatic hydrolysis, mass spectrometry and comparisons with standards. Cells, treated with these compounds, were assessed for viability and apoptosis and examined by western blotting. RESULTS:Gallate estersB2-G(2), B2-3G and B2-3'G significantly decreased LNCaP cell viability; however, B2 and gallic acid were ineffective. Furthermore, only B2-G(2) also significantly decreased cell growth. Decreases in cell viability were largely due to apoptosis induction with B2-G(2) and B2-3'G exhibiting comparable effects, whereas B2-3G was less effective. In mechanistic studies, B2-G(2) and B2-3'G treatments caused caspases-9 and -3 and PARP cleavage, and down-regulated Bcl-2, Bcl-Xl and androgen receptor levels. CONCLUSION: Together, our findings demonstrate anti-PCA efficacy of B2-G(2) and suggest that a gallate ester moiety at 3' position of procyanidin B2 contributes more extensively toward the biological activity of the di-gallate ester than esterification of position 3.
Authors: Ilya Raskin; David M Ribnicky; Slavko Komarnytsky; Nebojsa Ilic; Alexander Poulev; Nikolai Borisjuk; Anita Brinker; Diego A Moreno; Christophe Ripoll; Nir Yakoby; Joseph M O'Neal; Teresa Cornwell; Ira Pastor; Bertold Fridlender Journal: Trends Biotechnol Date: 2002-12 Impact factor: 19.536
Authors: Liwei Gu; Mark A Kelm; John F Hammerstone; Gary Beecher; Joanne Holden; David Haytowitz; Ronald L Prior Journal: J Agric Food Chem Date: 2003-12-03 Impact factor: 5.279
Authors: Suraj P Shrestha; John A Thompson; Michael F Wempe; Mallikarjuna Gu; Rajesh Agarwal; Chapla Agarwal Journal: Pharm Res Date: 2011-11-09 Impact factor: 4.200