Abstract 1591: Inhibition of prostate tumor growth by an extract from the muscadine grape

Abstract

Abstract Despite decades of advancements, cancer remains the second leading cause of mortality in the United States with an estimated 1.7 million new cases and over 600,000 deaths predicted for 2016, indicating a clear need for more effective chemotherapeutic and chemopreventive agents. While natural products derived from plants have served as an abundant source of anticancer agents, it is predicted that less than 2 percent of the plant species with medicinal value have been investigated. Muscadine grape (Vitis rotundifolia) skin and/or seed extracts are a popular nutraceutical supplement due to the high anti-oxidant, anti-inflammatory, and anti-proliferative effects of a distinct phytochemical composition of polyphenols and proanthocyanidins. The current study examines the effects of a proprietary muscadine grape extract formulation (MGE; Piedmont Research & Development Corp.) on the proliferation of prostate cancer cells and tumors. MGE inhibited the growth of human LnCaP prostate cancer cells, in both a time- and dose-dependent manner, as quantified using an IncuCyte Zoom Imaging system. Cell growth was reduced by 36.8% after a 5-day treatment with 20 µg/mL MGE compared to untreated cells (n = 6, p < 0.001). Athymic mice (male, 15-20 g, 5-6 weeks of age) were injected subcutaneously on the lower flank with 1.6 x 106 LNCaP cells, to assess the effect of the MGE in vivo. When the tumors reached 100 mm3, the mice were randomized and MGE was added to the drinking water at a concentration of 0.2 µg phenolics/mL (1.0 mg phenolics/mouse/day for a 25 g mouse); control mice drank untreated water. After 5 weeks, the mice were sacrificed and the tumors were weighed. The volume of prostate tumors growing in the flank of nude mice drinking water with MGE was markedly reduced compared to the size of the tumors from control mice [252.6 ± 61.73 mm3 (MGE) versus 765.2 ± 101.8 mm3 (control); n=6, p<0.001). Further, the weight of prostate tumors from mice drinking MGE was also significantly decreased [0.96 ± 0.14 g (control) as compared to 0.41 ± 0.11 g (MGE)], a reduction of 57% (p < 0.05). Five microns tumor sections were incubated with an antibody to CD34 and tumor vessels were identified by positive immunoreactivity and morphology. MGE reduced the number of blood vessels/field from 10.25 ± 0.9 to 7.10 ± 0.6 (p < 0.05), suggesting that the extract inhibits angiogenesis. Vascular endothelial growth factor (VEGF) and placental growth factor (PLGF) were measured by qPCR, to determine the effect of the extract on angiogenic factors. MGE reduced VEGF mRNA from 1.02 ± 0.06 to 0.72 ± 0.07 relative units (p < 0.05) and PLGF mRNA from 1.03 ± 0.11 to 0.63 ± 0.07 relative units (p < 0.05), providing additional evidence of an anti-angiogenic effect of the extract. Collectively, these results are the first to demonstrate that a novel MGE formulation reduces prostate tumor growth in a mouse model, by inhibiting angiogenesis, suggesting that MGE may be an effective treatment for prostate cancer. Citation Format: Patricia E. Gallagher, E. Ann Tallant. Inhibition of prostate tumor growth by an extract from the muscadine grape [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1591. doi:10.1158/1538-7445.AM2017-1591