Back to Search
Start Over
Identification of hematein as a novel inhibitor of protein kinase CK2 from a natural product library.
- Source :
- BMC Cancer; 2009, Vol. 9, Special section p1-10, 10p, 1 Chart, 5 Graphs
- Publication Year :
- 2009
-
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 IC<subscript>50</subscript> value of 0.55 µM. 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14712407
- Volume :
- 9
- Database :
- Complementary Index
- Journal :
- BMC Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 42408251
- Full Text :
- https://doi.org/10.1186/1471-2407-9-135