Quercetin Inhibits Colorectal Cancer Cells Induced-Angiogenesis in Both Colorectal Cancer Cell and Endothelial Cell through Downregulation of VEGF-A/VEGFR2

Abstract

Colorectal cancer (CRC) aggressiveness is caused by cancer angiogenesis which promotes the cancer growth and metastasis associated with poor prognosis and poor survival. The vascular endothelial growth factor-A (VEGF-A) and its receptor (VEGFR-2) form the major signaling pathway in cancer angiogenesis. This study aimed to investigate the anti-angiogenesis activity of quercetin in both colorectal cancer cells and endothelial cells. The tube formation of human vein endothelial cells (HUVECs) was determined by using conditioned media of HT-29 cells treated with quercetin co-cultured with HUVECs. The VEGF-A and NF-κB p65 protein expressions in the quercetin-treated HT-29 cells were determined by fluorescence assay and Western blot analysis. The VEGFR-2 protein expression in HUVECs was determined after they were co-cultured with the quercetin-treated HT-29 cells. Quercetin markedly decreased the HT-29 cell-induced angiogenesis in HUVECs. NF-κB p65 and VEGF-A protein expression were also inhibited by quercetin. Moreover, quercetin significantly inhibited VEGFR-2 expression and translocation in HUVECs after they were co-cultured with high dose quercetin-treated HT-29 cells. Taken together, quercetin had an anti-angiogenesis effect on VEGF-A inhibition related to the NF-κB signaling pathway in the HT-29 cells and reduced VEGFR-2 expression and translocation in HUVECs.

Keywords

• colorectal cancer
• angiogenesis
• quercetin
• NF-κB
• VEGF-A
• VEGFR-2