Ethyl pyruvate, an anti-inflammatory agent, inhibits tumor angiogenesis through inhibition of Akt and NF-kB signaling pathways.

A117

Inflammation-dependent angiogenesis seems to be a central force in tumor growth and expansion. Native immune cells recruited into tumors in turn stimulate the endothelial cells and are responsible for an indirect pathway of tumor vascularization. Ethyl pyruvate (EP) has been shown to have anti-inflammatory properties in numerous cell culture and animal studies. Here, we show for the first time that ethyl pyruvate exhibits strong anti-angiogenic activity. EP inhibits in vivo angiogenesis in mouse matrigel plug assay. EP also interferes with angiogenic cascade, including growth, invasion, migration and tube formation. To clarify the underlying mechanism of anti-angiogenic effects of ethyl pyruvate, we examined Akt and NF-kB pathway as a mechanistic link between angiogenesis and inflammation. The phosphorylation of Akt and the nuclear translocation of nuclear factor-kB (NF-kB) were reduced by EP. Furthermore, EP inhibited the expressions of endothelial and inducible nitric oxide synthase (NOS), leading to reduced production of nitric oxide (NO). Taken together, these data suggest that ethyl pyruvate has anti-angiogenic activity as well as anti-inflammatory activity via suppression of Akt and NF-kB signaling pathways. Therefore, we suggest that ethyl pyruvate can be a new multi-functional drug candidate for anti-angiogenesis and cancer therapy.