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论文类型：期刊论文

发表时间：2016-06-01

发表刊物：MOLECULAR & CELLULAR TOXICOLOGY

收录刊物：Scopus、SCIE

卷号：12

期号：2

页面范围：159-166

ISSN号：1738-642X

关键字：Ortho-topolin riboside; Acute myeloid leukemia; HL-60 cell line; Apoptosis

摘要：6-(2-hydroxybenzylamino)-9-D-ribofuranosylpurine (ortho-topolin riboside, oTR), a naturally occurring cytokinin and nucleoside analog has potential anticancer effects. However, the molecular mechanisms remain elusive. We found that oTR strongly inhibited Acute myeloid leukemia HL-60 cell proliferation, altered the cell cycle, induced cytochrome c release from mitochondria into the cytosol, and increased caspase-3 activity. Apoptosis was confirmed by DNA ladder formation following gel electrophoresis. These results indicated that oTR induced apoptosis through activation of the intrinsic mitochondrial pathway. Moreover, the apoptosis was significantly suppressed by the adenosine transporter inhibitor dipyridamole and adenosine kinase inhibitor A-134974. These data indicated that cellular uptake of oTR was an active process involving an adenosine transporter, and subsequently phosphorylated by an adenosine kinase. Taken together, Our study suggests that oTR is taken up by HL-60 cells, converted to the phosphorylated form, and induces apoptosis.