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박길홍,JaegolChoe,Hyo-JungChoo,박윤규,손정원,Meyoung-konKim 생화학분자생물학회 2002 Experimental and molecular medicine Vol.34 No.3
Previous reports raised question as to whether 8-chloro-cyclic adenosine 3,5-monophosphate (8-Cl-cAMP) is a prodrug for its metabolite, 8-Cl-adenos-ine which exerts growth inhibition in a broad spec-trum of cancer cells. The present study was cariedout to clarify overall cellular afects of 8-Cl-cAMPand 8-Cl-adenosine on SK-N-DZ human neuroblas-toma cells by systematically characterizing geneexpression using radioactive human cDNA microaray.Microarray was prepared with PCR-amplified cDNAof 2,304 known genes spotted on nylon membranes,employing 33P-labeled cDNAs of SK-N-DZ cells as aprobe. The expression levels of approximately 100cDNAs, representing about 8% of the total DNA ele-ments on the array, were altered in 8-Cl-adenosine- or8-Cl-cAMP-treated cells, respectively. The genome-wide expression of the two samples exhibited partialoverlaps; different sets of up-regulated genes butthe same set of down-regulated genes. 8-Cl-adenos-ine treatment up-regulated genes involved in difer-entiation and development (LIM protein, connexin26, neogenin, neurofilament triplet L protein andp21WAF1/CIP1) and immune response such as naturalkiller cells protein 4, and down-regulated onesinvolved in proliferation and transformation (trans-forming growth factor-b, DYRK2, urokinase-typeplasminogen activator and proteins involved in tran-scription and translation) which were in close paral-lel with those by 8-Cl-cAMP. Our results indicatedthat the two drugs shared common genomic path-ways for the down-regulation of certain genes, butused distinct pathways for the up-regulation of dif-ferent gene clusters. Based on the findings, we sug-gest that the anti-cancer activity of 8-Cl-cAMPresults at least in part through 8-Cl-adenosine. Thus,the systematic use of DNA arrays can provideinsight into the dynamic cellular pathways involvedin anticancer activities of chemotherapeutics.
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