%0 Journal Article %J BMC Cancer %D 2009 %T Identification of hematein as a novel inhibitor of protein kinase CK2 from a natural product library. %A Hung, Ming-Szu %A Xu, Zhidong %A Lin, Yu-Ching %A Jiang-Hua Mao %A Yang, Cheng-Ta %A Chang, Pey-Jium %A Jablons, David M %A You, Liang %K Adenosine Triphosphate %K Apoptosis %K Casein Kinase II %K Cell Growth Processes %K Cell Line, Tumor %K Dose-Response Relationship, Drug %K HCT116 Cells %K HeLa Cells %K Hematoxylin %K Humans %K Lung Neoplasms %K Neoplasms %K Protein Kinase Inhibitors %K Proto-Oncogene Proteins c-akt %K Substrate Specificity %X

BACKGROUND: Casein kinase 2 (CK2) is dysregulated in various human cancers and is a promising target for cancer therapy. To date, there is no small molecular CK2 inhibitor in clinical trial yet. With the aim to identify novel CK2 inhibitors, we screened a natural product library.

METHODS: We adopted cell-based proliferation and CK2 kinase assays to screen CK2 inhibitors from a natural compound library. Dose-dependent response of CK2 inhibitors in vitro was determined by a radioisotope kinase assay. Western blot analysis was used to evaluate down stream Akt phosphorylation and apoptosis. Apoptosis was also evaluated by annexin-V/propidium iodide (PI) labeling method using flow cytometry. Inhibition effects of CK2 inhibitors on the growth of cancer and normal cells were evaluated by cell proliferation and viability assays.

RESULTS: Hematein was identified as a novel CK2 inhibitor that is highly selective among a panel of kinases. It appears to be an ATP non-competitive and partially reversible CK2 inhibitor with an IC50 value of 0.55 muM. In addition, hematein inhibited cancer cell growth partially through down-regulation of Akt phosphorylation and induced apoptosis in these cells. Furthermore, hematein exerted stronger inhibition effects on the growth of cancer cells than in normal cells.

CONCLUSION: In this study, we showed that hematein is a novel selective and cell permeable small molecule CK2 inhibitor. Hematein showed stronger growth inhibition effects to cancer cells when compared to normal cells. This compound may represent a promising class of CK2 inhibitors.

%B BMC Cancer %V 9 %P 135 %8 2009 %G eng %1 http://www.ncbi.nlm.nih.gov/pubmed/19419583?dopt=Abstract %R 10.1186/1471-2407-9-135