@article {166, title = {Identification of hematein as a novel inhibitor of protein kinase CK2 from a natural product library.}, journal = {BMC Cancer}, volume = {9}, year = {2009}, month = {2009}, pages = {135}, abstract = {

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.

}, keywords = {Adenosine Triphosphate, Apoptosis, Casein Kinase II, Cell Growth Processes, Cell Line, Tumor, Dose-Response Relationship, Drug, HCT116 Cells, HeLa Cells, Hematoxylin, Humans, Lung Neoplasms, Neoplasms, Protein Kinase Inhibitors, Proto-Oncogene Proteins c-akt, Substrate Specificity}, issn = {1471-2407}, doi = {10.1186/1471-2407-9-135}, author = {Hung, Ming-Szu and Xu, Zhidong and Lin, Yu-Ching and Jiang-Hua Mao and Yang, Cheng-Ta and Chang, Pey-Jium and Jablons, David M and You, Liang} }