PMID: 18710613Aug 20, 2008Paper

Effects of mitoxantrone on the activity of human protein kinase CK2 holoenzyme

Ai zheng = Aizheng = Chinese journal of cancer
Chunmei LiNian-Ci Liang

Abstract

Protein kinase CK2, a highly conserved protein serine/threonine kinase that is ubiquitously distributed in eukaryotes, has a close relationship with human leukemia. Mitoxantrone is an effective drug used for acute leukemias. This study was to observe the effects of mitoxantrone on the activity of recombinant holoenzyme of human protein kinase CK2 and proliferation in human leukemia cell line HL-60. The CK2 holoenzyme composed of alphao and beta subunits was recombined in vitro. Subsequently, CK2 was treated with mitoxantrone at various concentrations, followed by addition of reacting liquid containing [gamma-32P] ATP. CK2 activity was measured by detecting the radioactivity of 32P transferred onto the substrates of CK2. The effect of mitoxantrone on the proliferation of HL-60 cells was detected by the trypan blue dye exclusion assay; the changes in the cell cycle were analyzed by flow cytometry (FCM); apoptosis was analyzed by FCM and DNA agarose gel electrophoresis; effects of the drugs on the intrinsic CK2 activity were measured by a specific CK2 peptide substrate. Mitoxantrone strongly inhibited the holoenzyme activity of recombinant human protein kinase CK2 (IC50=0.66 micromol/L). The inhibition of CKZ by mitoxantrone was c...Continue Reading

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