Abstract 3695: Oligonol, a novel lychee fruit-derived low-molecular weight procyanidin extract, inhibits angiogenesis: Implications for its use as angiopreventive agent against cancer

Abstract

Abstract Neo-angiogenesis, formation of new blood vessels from pre-existing vessels, is an essential hallmark for cancer growth and progression. Accordingly, several anti-angiogenic drugs including VEGF and VEGFR2 inhibitors have been either tested clinically or already approved by FDA for the treatment of various malignancies. Despite their strong anti-angiogenic efficacy, these drugs are costly, have significant side-effects and tumors quickly develop resistance, providing only marginal survival benefits. This scenario clearly warrants the need to identify non-toxic, affordable and effective alternative angiogenesis inhibitors to target cancer growth and progression. In this regard, an increasing number of natural compounds have shown anti-angiogenic activity with little or no side effects, and angioprevention of cancer through these chemopreventive agents is emerging as an exciting alternative approach. Accordingly, here, for the first time we investigated the anti-angiogenic efficacy of oligonol using human umbilical vein endothelial cells (HUVEC) as a model. Oligonol is a novel oligomerized low molecular weight procyanidin extract from lychee fruit and has shown good bioavailability in humans. Our results showed that oligonol (10-20 microgram/ml) strongly inhibits proliferation of HUVEC by 34-96%, 59-96% and 60% to complete inhibition after 24, 48 and 72 hrs of its exposure, respectively. In the studies examining its effect on cell cycle progression and apoptosis induction in HUVEC, we found that oligonol (10-20 microgram/ml) causes cell cycle arrest at G1 phase and induces apoptosis in HUVEC in a dose-dependent manner. Western blot analyses revealed that oligonol increases Cip1/p21 levels and Bad/Bcl2 ratio, decreases survivin and p-Akt levels, and activates caspase 3 and 9 followed by PARP cleavage. In other studies, oligonol (5-15 microgram/ml) strongly inhibited the capillary-like tube formation as well as disrupted pre-formed tubes by HUVEC on matrigel. Importantly, oligonol also inhibited VEGF-induced growth and tube formation by HUVEC. In addition, oligonol strongly inhibited the invasiveness of HUVEC in transwell assay and the migratory potential of HUVEC in wound healing assay by 40-95% and 58% to complete inhibition at 5, 10 & 15 microgram/ml doses, respectively. Importantly, we also observed that oligonol treatment inhibits phosphorylation of STAT3(Tyr705), Src(Tyr416) and FAK(Y576/577) which are known to regulate proliferation, migration and invasion of endothelial cells. Taken together, our findings clearly demonstrated the anti-angiogenic potential of oligonol, suggesting the use of this non-toxic and highly bioavailable agent for clinical cancer conditions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3695. doi:10.1158/1538-7445.AM2011-3695