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Identification of hematein as a novel inhibitor of protein kinase CK2 from a natural product library

Journal Article · · BMC Cancer
 [1];  [2];  [3];  [4];  [5];  [6];  [2];  [2]
  1. Univ. of California, San Francisco, CA (United States). Comprehensive Cancer Center. Dept. of Surgery. Thoracic Oncology Lab.; Chang Gung Memorial Hospital, Chiayi, Taiwan (Republic of China). Division of Pulmonary and Critical Care Medicine; Chang Gung University, Taoyuan, Taiwan (Republic of China). College of Medicine. Graduate Inst. of Clinical Medical Sciences; DOE/OSTI
  2. Univ. of California, San Francisco, CA (United States). Comprehensive Cancer Center. Dept. of Surgery. Thoracic Oncology Lab.
  3. Chang Gung Memorial Hospital, Chiayi, Taiwan (Republic of China). Division of Pulmonary and Critical Care Medicine; Chang Gung University, Taoyuan, Taiwan (Republic of China). College of Medicine. Graduate Inst. of Clinical Medical Sciences
  4. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division
  5. Chang Gung Memorial Hospital, Chiayi, Taiwan (Republic of China). Division of Pulmonary and Critical Care Medicine; Chang Gung University, Taoyuan, Taiwan (Republic of China). College of Medicine. Dept. of Respiratory Care
  6. Chang Gung University, Taoyuan, Taiwan (Republic of China). College of Medicine. Graduate Inst. of Clinical Medical Sciences
+ Show Author Affiliations
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 μM. In addition, hematein inhibited cancer cell growth partially through downregulation 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.
Research Organization:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC)
Sponsoring Organization:
National Institutes of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1626530
Alternate ID(s):
OSTI ID: 22386670
Journal Information:
BMC Cancer, Journal Name: BMC Cancer Journal Issue: 1 Vol. 9; ISSN 1471-2407
Publisher:
BioMed CentralCopyright Statement
Country of Publication:
United States
Language:
English

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Cited By (7)

Protein Kinase CK2, a Potential Therapeutic Target in Carcinoma Management journal January 2019
CK2 in Cancer: Cellular and Biochemical Mechanisms and Potential Therapeutic Target journal January 2017
Hematein, a casein kinase II inhibitor, inhibits lung cancer tumor growth in a murine xenograft model journal September 2013
Identification of compounds inhibiting prion replication and toxicity by removing PrP C from the cell surface journal July 2019
EGFR–PI3K–AKT–mTOR signaling in head and neck squamous cell carcinomas: attractive targets for molecular-oriented therapy journal November 2010
Casein kinases as potential therapeutic targets journal November 2015
Casein kinases as potential therapeutic targets text January 2015

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