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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.

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Abbreviations

AR:

androgen receptor

B2:

procyanidin B2

B2-G2 :

procyanidin B2-3,3′-di-O-gallate

B2-3′G:

procyanidin B2-3′-O-gallate

B2-3G:

procyanidin B2-3-O-gallate

GSE:

grape seed extract

PARP:

poly (ADP-ribose) polymerase

PCA:

prostate cancer

SEC:

size-exclusion chromatography

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ACKNOWLEDGEMENTS

This study was supported by the National Cancer Institute, NIH RO1 grant CA091883.

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Author notes

  1. Shen-Chieh Chou

    Present address: Research Center for Biodiversity and Graduate Institute of Ecology and Evolutionary Biology, China Medical University, Taichung, 40402, Taiwan

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, C238- P15, Research 2, Room 3122, 12700 19th Ave., Aurora, Colorado, 80045, USA

    Shen-Chieh Chou, Manjinder Kaur, John A. Thompson, Rajesh Agarwal & Chapla Agarwal

  2. University of Colorado Cancer Center, University of Colorado Denver, Aurora, Colorado, 80045, USA

    John A. Thompson, Rajesh Agarwal & Chapla Agarwal

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  1. Shen-Chieh Chou
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Correspondence to Chapla Agarwal.

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Chou, SC., Kaur, M., Thompson, J.A. et al. Influence of Gallate Esterification on the Activity of Procyanidin B2 in Androgen-Dependent Human Prostate Carcinoma LNCaP Cells. Pharm Res 27, 619–627 (2010). https://doi.org/10.1007/s11095-009-0037-6

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