Inhibitory influence of natural flavonoids on human protein kinase CK2 isoforms: effect of the regulatory subunit

CK2 is a pleiotropic, constitutively active protein kinase responsible for the phosphorylation of more than 300 physiological substrates. Typically, this enzyme is found in tetrameric form consisting of two regulatory subunits CK2 beta and two catalytic subunits CK2 alpha or CK2 alpha'. Several natural occurring flavonoids were tested for their ability to inhibit both CK2 holoenzymes, CK2 alpha(2)beta(2) and CK2 alpha'(2)beta(2). We identified few substances selectively inhibiting only the alpha' subunit. Other compounds showed similar effect towards all four isoforms. In some cases, like chrysoeriol, pedalitin, apigenin, and luteolin, the alpha(2)beta(2) holoenzyme was at least six times better inhibited than the free alpha subunit. Otherwise, we have found a luteolin derivative decreased the kinase activity of CK2 alpha' with an IC50 value of 0.8 mu M, but the holoenzyme only with 9.5 A mu M.