Chlorogenic acid suppresses neutrophil recruitment to tumors by inducing apoptosis and reverse migration

Neutrophilic inflammation plays a vital role in cancer recurrence and metastasis. One therapeutic strategy is to clear neutrophils from the inflammatory site by inducing apoptosis or reverse migration. Bacteria-mediated cancer therapy (BCT) regulates neutrophil infiltration and shows robust anti-tumor activity. Chlorogenic acid, a natural compound found in coffee, shows anti-inflammatory activity. Here, we used live-cell imaging of zebrafish to show that chlorogenic acid clears neutrophils from inflammatory sites by inducing apoptosis and reverse migration. The effect is mediated by inhibiting phosphorylation of ERK and AKT. In addition, chlorogenic acid abrogates △ppGpp S. Typhimurium -induced neutrophil recruitment to tumors in a mouse model of colon cancer, thereby prolonging bacterial colonization.