Inhibition of protein kinase CKII activity by euchrestaflavanone B purified from Cudrania tricuspidata.
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.
Kim
Soon-Hee
SH
Department of Biochemistry, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Korea.
Yoon
Soo-Hyun
SH
Lee
Byong Won
BW
Park
Ki Hun
KH
Kim
Young Ho
YH
Bae
Young-Seuk
YS
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D047390:Casein Kinase II / Q000037:antagonists & inhibitors*; D044950:Flavanones / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D029586:Moraceae / Q000737:chemistry*; D018517:Plant Roots / Q000737:chemistry; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D020298:U937 Cells
D000972:Antineoplastic Agents, Phytogenic; D044950:Flavanones; D047428:Protein Kinase Inhibitors; C508749:euchrestaflavanone B; D047390:Casein Kinase II