Inhibition of protein kinase CKII activity by euchrestaflavanone B purified from Cudrania tricuspidata.

Abstract

The CKII (EC 2.7.1.37) inhibitory compound was purified from the root barks of Cudrania tricuspidata and identified as (2S)-2-[2,4-dihydroxy-5-(3-methyl-but-2-enyl)-phenyl]-5,7-dihyroxy-6-(3-methyl-but-2-enyl)chroman-4-one (euchrestaflavanone B). Euchrestaflavanone B was shown to inhibit the phosphotransferase activity of CKII with IC50 of about 78 microM. Steady-state studies revealed that euchrestaflavanone B acted as a competitive inhibitor with respect to the substrate ATP. A value of 16.4 microM was obtained for the apparent Ki. Concentration of 0.8 microM euchrestaflavanone B caused 50% growth inhibition of human cancer cells U937 and HeLa. Euchrestaflavanone B-induced cell death was characterized with the cleavage of poly(ADP-ribose) polymerase and procaspase-3, indicating that the inhibitor triggered apoptosis. Because protein kinase CKII is involved in cell proliferation and oncogenesis, these results suggest that euchrestaflavanone B may function by inhibiting oncogenic disease, at least in part, through the inhibition of CKII activity.

• Authors: Soon-Hee Kim, Soo-Hyun Yoon, Byong Won Lee, Ki Hun Park, Young Ho Kim, Young-Seuk Bae
• Journal: Oncology research (Oncol Res) Vol. 15 Issue 6 Pg. 327-32 ( 2005) ISSN: 0965-0407 [Print] United States
• PMID: 16408697 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Flavanones
• Protein Kinase Inhibitors
• euchrestaflavanone B
• Casein Kinase II

Topics

• Antineoplastic Agents, Phytogenic (chemistry, pharmacology)
• Apoptosis (drug effects)
• Casein Kinase II (antagonists & inhibitors)
• Flavanones (pharmacology)
• HeLa Cells
• Humans
• Moraceae (chemistry)
• Plant Roots (chemistry)
• Protein Kinase Inhibitors (pharmacology)
• U937 Cells