Tumor growth and metastasis depend on angiogenesis triggered by chemical signals, such as vascular endothelial growth factor (VEGF), released from tumor cells. Therefore, the specific perturbation of angiogenesis has been considered a powerful strategy for the treatment of cancer. Herein, we report that tricin, 4',5,7-trihydroxy-3',5'-dimethoxyflavone, exhibits potent antiangiogenic activity in vitro. Tricin effectively suppressed the proliferation as well as VEGF-induced invasion and tube formation of human umbilical vein endothelial cells (HUVECs) at subtoxic doses. Furthermore, tricin significantly inhibited the angiogenesis of the chorioallantoic membrane from growing chick embryos without showing cytotoxicity. We also found that tricin blocked tumor cellinduced angiogenesis. Notably, tricin downregulated not only the VEGFR2 signal transduction by reducing reactive oxygen species (ROS) generation in endothelial cells, but also the expression of VEGF by inhibiting hypoxia inducible factor-1α (HIF-1α) accumulation in tumor cells. Moreover, combined treatment with tricin and bevacizumab, an anti-VEGF drug, ameliorated the antiangiogenic effect of bevacizumab. Taken together, our findings demonstrate for the first time that tricin possesses promising antiangiogenic potential and thus may be applied to anticancer therapy by targeting tumor angiogenesis.
Bibliographical noteFunding Information:
We are grateful to Yonghyo Kim for his help with the CAM assay. The present study was carried out with the support of 'Cooperative Research Program for Agriculture Science and Technology Development (Project No. PJ01188001)' Rural Development Administration, Republic of Korea, the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2014R1A1A2057902), and the Brain Korea 21 Plus Project, Republic of Korea.
All Science Journal Classification (ASJC) codes
- Cancer Research