Abstract 5648: Influence of gallate esterification on the activity of procyanidin B2 in androgen-dependent human prostate carcinoma LNCaP cells
Authors: Manjinder Kaur, Shen-Chieh Chou, John A. Thompson, Rajesh Agarwal, Chapla Agarwal
Journal: Cancer Research (2010)

Abstract Prostate cancer (PCA) is the most common cancer in elderly men with one out of six men afflicted with this malignancy in the United States. In spite of improvements in diagnostic and therapeutic strategies for PCA, prognosis of this malignancy remains poor at advanced stages suggesting that newer preventive/interventive strategies are required to control this malignancy. Plant based therapies are often used as alternative and complementary treatments for various diseases including cancer. Grape seed extract (GSE) is a rich source of procyanidins and is used as a health supplement in United States. In our previously published studies, we have demonstrated chemopreventive efficacy of this extract per se and of biologically active constituents present in the extract such as gallic acid against PCA. We also demonstrated anti-cancer efficacy of B2-3,3′-di-O-gallate (B2-G2), a di-gallate ester of procyanidin B2 against androgen-independent human PCA DU145 cells. Present study assessed the influence of gallate esterification on the anti-cancer activity of procyanidin B2 (B2) in human PCA 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. Since, androgen receptor (AR) is recognized as an important molecular target in early as well as advanced stages of PCA, in the present study, we used human prostate carcinoma LNCaP cells that harbor functional AR and are dependent on androgen for their growth, to investigate the anticancer activity of these compounds. All these compounds were isolated from grape seed extract (GSE) following several chromatographic steps and structures determined by a combination of enzymatic hydrolysis, mass spectrometry and comparisons with standards. We observed that treatment of LNCaP cells with 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 AR levels. Taken 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. This study was supported by the National Cancer Institute, NIH RO1 grant CA091883. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5648.