PO-316 Isoquercetin: a novel agent to increases VASH1 and suppress colon cancer

Abstract

IntroductionAngiogenesis represents an important factor supporting the growth and propagation of many tumours; however, current antiangiogenesis agents exhibit limited efficacy or elevated adverse effects. As natural plant-based products with numerous beneficial physiologic effects, flavonoids represent attractive alternatives as cancer therapeutics. To the best of our knowledge, this study represents the first demonstration that the flavonoid isoquercetin (Q3G) functions as a novel inhibitor of angiogenesis in colorectal cancer by targeting vasohinibin 1 (VASH1). Vasohibin-1 (VASH1) is an endogenous angiogenesis inhibitor. However, the clinical relevance of VASH1 in colon cancer and its regulations on cancer angiogenesis and cancer cell biological characteristics are still unknown. The aim of this study was to evaluate the flavonoid isoquercetin (Q3G) as a novel VASH1-targeted inhibitor of angiogenesis in colorectal cancer.Material and methodsBalb-c nude mice were implanted with human colon adenocarcinoma HT-29 cells. The tumour volume was monitored daily. Following euthanasia, tumours were subjected to histological analysis (histologic grade, microvessel count) and immunohistochemical determination of VASH1 expression. Statistical analysis of the data (ANOVA and polynomial regression) adopted a 5% significance level.Results and discussionsWe identified that acute but not prophylactic administration of Q3G in a mouse xenotransplant tumour model Q3G increased VASH1 expression, decreased vascular proliferation, and inhibited tumour growth. Our studies suggest that Q3G therefore represents a vascular disrupting agent, inhibiting tumour growth by limiting tumour blood supply and neovascularization through the upregulation of the angiogenesis inhibitory factor, VASH1.ConclusionThus, Q3G targeting of VASH1 expression may serve as a novel antiangiogenesis strategy for treating colorectal cancer.