casein-kinase-ii and baicalein

A series of halogenated derivatives of natural flavonoids: baicalein and chrysin were designed and investigated as possible ligands for the catalytic subunit of tumor-associated human kinase CK2. Thermal shift assay method, in silico modeling, and high-performance liquid chromatography-derived hydrophobicity together with IC

Topics: Antineoplastic Agents; Casein Kinase II; Cell Line, Tumor; Drug Screening Assays, Antitumor; Flavanones; Flavonoids; Halogenation; Humans; Magnetic Resonance Spectroscopy; Models, Molecular; Protein Kinase Inhibitors; Structure-Activity Relationship

Protein kinase CK2 is a ubiquitous and pleiotropic Ser/Thr protein kinase in eukaryotic cells. CK2 activity has been shown to be markedly elevated in solid tumors and leukemia cells. Its alpha or alpha' gene is a protooncogene. CK2 is attracting increasing attention as a potential target for anti-neoplastic. This study was to search specific CK2 inhibitors in tumor cells through observation of the inhibitory effects of baicalein on recombinant human protein kinase CK2 holoenzyme and its kinetics in vitro.. Recombinant human protein kinase CK2 alpha' and beta subunits were cloned and expressed by gene engineering, and purified to homogeneous. These 2 subunits were mixed at equal molar ratio to reconstitute CK2 holoenzyme. The CK2 activity was evaluated by detecting radioactivity of 32P of [gamma-32P]ATP which was incorporated into the substrate in various conditions.. Baicalein was shown to strongly inhibit the holoenzyme activity of CK2 with IC50 of 2.54 micromol/L. Kinetic studies of baicalein on CK2 showed that baicalein acted as an inhibitor of noncompetitive with ATP(KI=7.73 micromol/L) and mixed types with casein(KI=3.07 micromol/L).. Baicalein is an effective inhibitor of protein kinase CK2 in vitro.

Topics: Casein Kinase II; Enzyme Inhibitors; Flavanones; Holoenzymes; Humans; Kinetics; Plants, Medicinal; Recombinant Proteins; Scutellaria baicalensis