Influence of gallate esterification on the activity of procyanidin B2 in androgen-dependent human prostate carcinoma LNCaP cells.

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-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.

• Authors: Shen-Chieh Chou, Manjinder Kaur, John A Thompson, Rajesh Agarwal, Chapla Agarwal
• Journal: Pharmaceutical research (Pharm Res) Vol. 27 Issue 4 Pg. 619-27 (Apr 2010) ISSN: 1573-904X [Electronic] United States
• PMID: 20162340 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antineoplastic Agents, Phytogenic
• Biflavonoids
• Proanthocyanidins
• Proto-Oncogene Proteins c-bcl-2
• procyanidin B2
• Catechin
• Poly(ADP-ribose) Polymerases
• Caspases

Topics

• Antineoplastic Agents, Phytogenic (chemistry, isolation & purification, pharmacology)
• Apoptosis (drug effects)
• Biflavonoids (chemistry, isolation & purification, pharmacology)
• Carcinoma (drug therapy)
• Caspases (metabolism)
• Catechin (chemistry, isolation & purification, pharmacology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Humans
• Male
• Poly(ADP-ribose) Polymerases (metabolism)
• Proanthocyanidins (chemistry, isolation & purification, pharmacology)
• Prostatic Neoplasms (drug therapy)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Seeds (chemistry)
• Vitis (chemistry)