Abstract
An attempt was made to elucidate the molecular target for the antitumor effects of cordycepin (3′-deoxyadenosine) using non-selective and selective adenosine A1, A2a, A2b and A3 receptor agonists and antagonists. Although adenosine and 2′-deoxyadenosine (up to 100 μM) had no effect, cordycepin showed remarkable inhibitory effects on the growth curves of B16-BL6 mouse melanoma (IC50=39 μM) and mouse Lewis lung carcinoma (IC50=48 μM) cell lines in vitro. Among the adenosine receptor agonists and antagonists used (up to 100 μM), only 2-chloro-N6-(3-iodobenzyl)-adenosine-5′-N-methyluronamide (Cl-IB-MECA), a selective adenosine A3 receptor agonist, notably inhibited the growth of both mouse tumor cell lines (B16-BL6; IC50=5 μM, LLC; 14 μM). In addition, the tumor growth inhibitory effect of cordycepin was antagonized by 3-ethyl 5-benzyl 2-methyl-6-phenyl-4-phenylethynyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS1191), a selective adenosine A3 receptor antagonist. These results suggest that cordycepin exerts inhibitory effects on the growth of mouse melanoma and lung carcinoma cells by stimulating adenosine A3 receptors on tumor cells.
- Cordycepin (3′-deoxyadenosine)
- adenosine A3 receptor
- B16-BL6 mouse melanoma cells
- Lewis lung carcinoma cells
Footnotes
- Received September 8, 2005.
- Accepted November 22, 2005.
- Copyright© 2006 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved