Antitumor Effect of Cordycepin (3′-Deoxyadenosine) on Mouse Melanoma and Lung Carcinoma Cells Involves Adenosine A3 Receptor Stimulation

An attempt was made to elucidate the molecular target for the antitumor effects of cordycepin (3′-deoxyadenosine) using non-selective and selective adenosine A 1 , A 2a , A 2b and A 3 receptor agonists and antagonists. Although adenosine and 2′-deoxyadenosine (up to 100 μM) had no effect, cordy...

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Bibliographic Details
Published in:Anticancer research 2006-01, Vol.26 (1A), p.43-47
Main Authors: NAKAMURA, Kazuki, YOSHIKAWA, Noriko, YAMAGUCHI, Yu, KAGOTA, Satomi, SHINOZUKA, Kazumasa, KUNITOMO, Masaru
Format: Article
Language:English
Subjects:
Adenosine - analogs & derivatives
Adenosine - pharmacology
Adenosine A3 Receptor Agonists
Adenosine A3 Receptor Antagonists
Animals
Antineoplastic Agents - pharmacology
Biological and medical sciences
Carcinoma, Lewis Lung - drug therapy
Carcinoma, Lewis Lung - pathology
Cell Growth Processes - drug effects
Cell Line, Tumor
Deoxyadenosines - pharmacology
Dermatology
Dihydropyridines - pharmacology
Drug Interactions
Medical sciences
Melanoma, Experimental - drug therapy
Melanoma, Experimental - pathology
Mice
Stimulation, Chemical
Tumors
Tumors of the skin and soft tissue. Premalignant lesions
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Summary:An attempt was made to elucidate the molecular target for the antitumor effects of cordycepin (3′-deoxyadenosine) using non-selective and selective adenosine A 1 , A 2a , A 2b and A 3 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 (IC 50 =39 μM) and mouse Lewis lung carcinoma (IC 50 =48 μM) cell lines in vitro. Among the adenosine receptor agonists and antagonists used (up to 100 μM), only 2-chloro-N 6 -(3-iodobenzyl)-adenosine-5′-N-methyluronamide (Cl-IB-MECA), a selective adenosine A 3 receptor agonist, notably inhibited the growth of both mouse tumor cell lines (B16-BL6; IC 50 =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 A 3 receptor antagonist. These results suggest that cordycepin exerts inhibitory effects on the growth of mouse melanoma and lung carcinoma cells by stimulating adenosine A 3 receptors on tumor cells.
ISSN:0250-7005
1791-7530