Orthotopolin riboside induces apoptosis in Acute

Authors: Li Wang Dong Li Yu Han Wen Zhang Lei Yu He Lei Wu

Publish Date: 2016/06/28

Volume: 12, Issue: 2, Pages: 159-166

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Abstract

62hydroxybenzylamino9Dribofuranosylpurine orthotopolin 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 HL60 cell proliferation altered the cell cycle induced cytochrome c release from mitochondria into the cytosol and increased caspase3 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 A134974 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 HL60 cells converted to the phosphorylated form and induces apoptosis

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