Adenosine receptor antagonism causes inhibition of angiogenic activity of human ovarian cancer cells.
Angiogenesis, new blood vessels development, is an important process involved in ovarian cancer growth and metastasis. Adenosine is a known mediator of angiogenesis in hypoxic tissues. Theobromine, adenosine receptor antagonist, 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 angiogenic activity of ovarian cancer cells as well as CD45 positive lymphocytes isolated from peritoneal ascitic fluid of ovarian cancer patients. Using synthetic adenosine receptor antagonists: 8-phenyl-theophylline and 8-cyclopentyl-1,3 dipropylxantine we established that antiangiogenic properties of theobromine are dependent on its interaction with A2 adenosine receptor. Our observations were confirmed in full suspensions of ascitic cells as well as in isolated cancer cells and CD45 lymphocytes. We postulate that A2 receptor antagonism may diminish angiogenesis induced by hypoxia in different cancer tissues and may find a place in future cancer therapy.
Barcz
E
E
First Department of Obstetrics and Gynaecology, The Medical University of Warsaw, 02-015 Warsaw, Poland.
Sommer
E
E
Janik
P
P
Marianowski
L
L
Skopinska-Rózewska
E
E
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001202:Ascitic Fluid / Q000473:pathology; D005260:Female; D006801:Humans; D017493:Leukocyte Common Antigens / Q000502:physiology; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D010051:Ovarian Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000473:pathology; D010641:Phenotype; D058915:Purinergic P1 Receptor Antagonists; D013805:Theobromine / Q000494:pharmacology*; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine; D013806:Theophylline; C028322:8-phenyltheophylline; D017493:Leukocyte Common Antigens; D013805:Theobromine