Adenosine receptor antagonism causes inhibition of angiogenic activity of human ovarian cancer cells

Angiogenesis, new blood vessels development, is an important process involv ed in ovarian cancer growth and metastasis. Adenosine is a known mediator o f angiogenesis in hypoxic tissues. Theobromine, adenosine receptor antagoni st, exerts antiangiogenic properties in many types of tumors in Balb/c mice cutaneous angiogenesis assay. The aim of the present study was to evaluate the mechanism of its action. We showed that theobromine inhibits angiogeni c activity of ovarian cancer cells as well as CD45 positive lymphocytes iso lated from peritoneal ascitic fluid of ovarian cancer patients. Using synth etic adenosine receptor antagonists: 8-phenyl-theophylline and 8-cyclopenty l-1,3 dipropylxantine we established that antiangiogenic properties of theo bromine are dependent on its interaction with A2 adenosine receptor. Our ob servations were confirmed in full suspensions of ascitic cells as well as i n isolated cancer cells and CD45 lymphocytes. We postulate that A2 receptor antagonism may diminish angiogenesis induced by hypoxia in different cance r tissues and may find a place in future cancer therapy.