Abstract
Tumor cells trigger angiogenesis through the expression of angiogenic factors. Vasohibins (VASHs) are a family of peptides that regulate angiogenesis. Flavonoids have antiproliferative antitumor properties; however, few studies have highlighted their antiangiogenic potential. This study evaluated the flavonoid isoquercetin (Q3G) as an antitumor compound related to colon cancer vascularization and regulation of VASH1 and 2. Mice bearing xenogeneic colon cancer (n = 15) were divided into 3 groups: Q3G-treated (gavage, daily over a week), bevacizumab-treated (intraperitoneal, single dose), or untreated animals. Tumor growth, histological characteristics, blood vessel volume, and VASH1 and 2 expressions were analyzed. Q3G impaired tumor growth and vascularization, upregulated VASH1, and downregulated VASH2 in comparison to untreated animals. Mice treated with Q3G showed approximately 65% fewer blood vessels than untreated animals and 50% fewer blood vessels than mice treated with bevacizumab. Thus, we show that Q3G has antitumor activity, impairs vascularization, and differentially modulates VASH1 and 2 expressions in colon cancer.
Highlights
Angiogenesis is characterized by the establishment of new blood vessels (BV) through stimulation of endothelial proliferation
This study evaluated the flavonoid isoquercetin (Q3G) as an antitumor compound related to colon cancer vascularization and regulation of VASH1 and 2
Mice treated with Q3G showed approximately 65% fewer blood vessels than untreated animals and 50% fewer blood vessels than mice treated with bevacizumab
Summary
Angiogenesis is characterized by the establishment of new blood vessels (BV) through stimulation of endothelial proliferation. The steps involved in angiogenesis include endothelial cell (EC) proliferation, sprouting, migration, tube formation, vessel remodeling, and pruning. Angiogenesis is a complex and multifactorial process that includes, but is not limited to, (i) stimulation by pro-angiogenic factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and transforming growth factor-beta (TGF-β); (ii) repression by anti-angiogenic factors (angiostatin, endostatin, and vasoinhibin); and (iii) regulation by non-angiogenic factors (O2 consumption rate and nutrient deprivation threshold for early necrosis) [2,3,4]. It increases tubulin levels and thereby suppresses endocytosis, whereas VASH2 is proangiogenic and exhibits tubulin carboxypeptidase activity related to microtubule functions and facilitates tubulin detyrosination. VASH1 levels are low in proliferating ECs at the sprouting front and high in non-proliferating ECs at the angiogenesis termination zone where VASH1 possibly interrupts angiogenesis. High levels of VASH2 are found at the sprouting front and lower levels at the termination zone [9]
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