Chlorogenic acid suppresses angiogenesis in 4T1 breast tumors via Cox-2, Vegf, and Mmp-9 downregulation

Background and purpose: Angiogenesis, as a physiological process, plays a key role in the development of invasive tumors. However, polyphenol compounds such as chlorogenic acid (CGA) can help reduce the risk of metastasis. This study explored the anti-angiogenic properties of CGA in a metastatic tumor model. Experimental approach: Forty female BALB/c mice were randomly divided into 5 groups, including saline, receiving normal saline; breast cancer (BC), receiving 4T1 cells and normal saline; CGA group, receiving CGA solution; PR group, receiving simultaneously 4T1 cells and CGA; treatment group (TM), receiving CGA after tumor induction. The treatment period was 14 days. The anti-angiogenic effects of CGA were examined using the H&E and TB staining in breast, liver, and lung tissues of the metastatic tumor model. Real-time RT- PCR was also conducted to determine the expression of Vegf, Cox-2, and Mmp-9 genes in tumor vessels and metastatic tissues. Findings/Results: Histomorphological evaluations demonstrated a significant reduction in the number of all types of breast vessels and many vessels of lung tissue in the TM group compared with the BC group. Also, the diameter of sinusoid capillaries and veins of liver tissue significantly decreased with the administration of CGA compared with the BC group. Moreover, real-time RT-PCR results showed that CGA administration downregulated the expression of Cox-2 , Vegf , and Mmp-9 levels compared with the BC group, significantly. Conclusion and implications: CGA plays an important role in inhibiting angiogenesis by decreasing the expression of Cox-2, Vegf, and Mmp-9 genes. It could improve the invasion of 4T1 breast cancer tumors in BALB/c mice.