, Volume 27, Issue 4, pp 619-627

Influence of Gallate Esterification on the Activity of Procyanidin B2 in Androgen-Dependent Human Prostate Carcinoma LNCaP Cells

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Abstract

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-G2), 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-G2, B2-3G and B2-3′G significantly decreased LNCaP cell viability; however, B2 and gallic acid were ineffective. Furthermore, only B2-G2 also significantly decreased cell growth. Decreases in cell viability were largely due to apoptosis induction with B2-G2 and B2-3′G exhibiting comparable effects, whereas B2-3G was less effective. In mechanistic studies, B2-G2 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-G2 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.