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KMID : 0545120060160091384
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Journal of Microbiology and Biotechnology
2006 Volume.16 No. 9 p.1384 ~ p.1391
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Identification of 3'-Hydroxymelanetin and Liquiritigenin as Akt Protein Kinase Inhibitors
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Yang Hye-Young
Lee Hong-Sub
Ko Jong-Hee
Yeon Seung-Woo
Kim Tae-Yong
Hwang Bang-Yeon
Kang Sang-Sun
Chun Jae-Sun
Hong Soon-Kwang
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Abstract
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The signal transduction system is one of the most important devices involved in maintaining life, and many protein kinases are included in the cellular signal transduction system. Finding a protein kinase inhibitor is very valuable, as it can be used to study cell biology and applied to pharmaceuticals. For the efficient and rapid screening of protein kinase inhibitors, two assay systems were combined; the nonradioactive protein kinase assay system that uses an FITC-labeled IRS-2 peptide and the cell-based paper disc assay system that uses Streptomyces griseus as the indicator strain. Among 330 kinds of herb extracts tested, the extract of Dalbergia odorifera exhibited the strongest inhibitory activity in the two assay systems and was selected for further isolation. Based on solvent extraction and many steps of chromatography, seven compounds were finally separated to homogeneity and their structures determined by 1H and 13C NMR spectroscopies. Four were to be flavonoids and identified as butin (C15H12O5, Mw=272.07), 3'-hydroxymelanetin (C16H12O6, Mw=300.06), liquiritigenin (C15H12O4, Mw=256.07), and 2'-hydroxyformononetin (C16H12O5, Mw=284.07). 3'-Hydroxymelanetin inhibited the phosphorylation of the GSK3 protein by Akt to 37% at a concentration of 10 μg/ml and showed the strongest cytotoxicity (ED50<50 μg/ml) against the human cancer cell line HCT116. Under the same conditions, liquiritigenin also inhibited the phosphorylation of GSK3 by Akt to 26%, and its cytotoxicity against the HCT116 cell line was lower than 100 μg/ml.
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KEYWORD
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Akt inhabitor, nonradioactive protein, kinase assay, cell-based paper disc
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