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Anticancer and antiangiogenic effects of phenolic acids on Ehrlich ascites tumor

Phenolic acids are plants polyphenols that are considered beneficial because of their potential protective role in the pathogenesis of multiple diseases associated to oxidative stress such as cancer, cardiovascular and neurodegenerative diseases. Anticancer mechanisms, anti-inflammatory, antioxidant and antiproliferative activities of phenolic acids like caffeic (CA), gallic (GA) and tannic (TA) acids are associated with induction of detoxification enzymes and inhibition of bioactive enzymes. Vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) are proangiogenic factors which play an important role in the invasion, metastasis and angiogenesis of cancer cells. Therefore, VEGF and MMPs are one of the targets for agents to suppress their expression and/or activities and that could inhibit the migration and invasion of cancer cells. The aim of this study was to investigate the molecular mechanisms of CA, GA and TA in the inhibition of angiogenesis and growth of Ehrlich ascites tumor (EAT) in mouse. EAT cells (2.5 x 106) were injected intraperitoneally (i.p.) in Swiss albino mice. One day after tumor inoculation, mice were injected i.p. with caffeic acid (CA) and gallic acid (GA) at dose of 40 and 80 mg/kg bw and tannic acid (TA) at dose of 5 and 10 mg/kg bw during 10 days. On day 14, we have analyzed the ascites volume, the total number of tumor cells in the peritoneal cavity, the microvessel density, the functional activity of macrophages, cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9). CA at dose of 80 mg/kg bw has the highest inhibitory effect on reduced ascites secretion and number of tumor cells. The biggest inhibition of COX-2 activity showed CA 80 mg/kg bw and TA 10 mg/kg bw which correlates with the increased activation of macrophages in ascites fluid, reduced number of blood vessels in peritoneum and decreased activity of MMP-2 in tumor cells. At the same time, TA 5 mg/kg bw significantly reduces level of VEGF in tumor cells. CA 40 mg/kg bw and GA 80 mg/kg bw demonstrated the highest inhibitory effect on activity of MMP-9 in tumor cells. Caffeic, gallic and tannic acids are able to suppress angiogenesis and tumor growth in Ehrlich ascites tumor and thus they may be a potential chemotherapeutic agents for cancer.

Phenolic acids, EAT tumor, angiogenesis, VEGF, MMPs, COX-2

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