casein-kinase-ii and chrysin

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

To investigate whether inhibitory effect of chrysin on sphere formation of ovarian cancer stem-like cells(spheroids derived from human ovarian cancer SKOV3 cell line ) is involved in the down-regulating of the protein expression of casein kinase CK2α.. SKOV3-derived ovarian cancer stem-like cells obtained by suspension culture in stem cell-condition medium using ultra-low adhesion plate were treated with various concentrations (5.0, 10.0 and 20.0 μmol/L) of chrysin. Sphere formation assay was used to determine the sphere forming rate of SKOV3-derived ovarian cancer stem-like cells. Western blot was used to analyze the protein expressions of CK2α and cancer stem cell markers CD133 and CD44. Silence of CK2α by siRNA and ectopic expression of CK2α by transfection with pcDNA3.1-CK2α plasmid were used to explore the mechanism underlying the effect of chrysin on sphere formation of SKOV3-derived ovarian cancer stem-like cells.. Chrysin (5.0, 10.0 and 20.0 μmol/L) significantly reduced the sphere forming rate of SKOV3-derived ovarian cancer stem-like cells, in a concentration-dependent manner (22.3%±2.5% vs 14.7%±2.1%, 8.6%± 1.7% and 3.8% ± 1.1% respectively; P<0.05). In addition, chrysin (5.0, 10.0 and 20.0 μmol/L) obviously down-regulated the protein expressions of CK2α, CD133 and CD44 in SKOV3-derived ovarian cancer stem-like cells. In combination with CK2α siRNA transfection and chrysin synergistically decreased sphere formation (P<0.05) and the protein expressions of CK2α, CD133 and CD44 in SKOV3-derived ovarian cancer stem-like cells. However, transfection with pcDNA3.1-CK2α plasmid attenuated inhibitory effects of chrysin on sphere formation capability and the expressions of CK2α, CD133 and CD44 of SKOV3-derived ovarian cancer stem-like cells.. Down-regulation of CK2α protein expression is involved in the inhibition effect of chrysin on the sphere formation capability of SKOV3-derived ovarian cancer stem-like cells.

Topics: Casein Kinase II; Cell Line, Tumor; Down-Regulation; Female; Flavonoids; Humans; Hyaluronan Receptors; Neoplastic Stem Cells; Ovarian Neoplasms; RNA, Small Interfering; Transfection

The identification of cellular factors that are required to complete various steps of the HIV-1 life cycle may lead to the development of new therapeutics. One key step, transcription from the integrated provirus, is inhibited by members of two distinct classes of compounds, the flavonoids and the benzothiophenes, via an unknown mechanism, possibly involving a cellular factor. A marked specificity toward inhibiting HIV-1 transcription is evidenced by the ability of drug-treated cells to retain their proliferative and differentiation capabilities. In addition, the compounds do not impede the activation and function of the transcriptional factor NF-kappaB. Here we report on the identification of several cellular proteins that mediate the HIV-1 transcriptional inhibitory property of the flavonoid chrysin. Chemical and immunologic analyses identified these cellular proteins as the individual subunits of casein kinase II (CKII). Though structurally unrelated to chrysin, an HIV-1 inhibitory benzothiophene also bound selectively to CKII. Both chrysin and the benzothiophenes inhibited human recombinant CKII enzymatic activity and showed competitive kinetics with respect to ATP, analogous to the classic CKII inhibitor 5, 6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB). Moreover, DRB potently inhibited HIV-1 expression in chronically infected cells. CKII may regulate HIV-1 transcription by phosphorylating cellular proteins involved in HIV-1 transactivation that contain multiple CKII phosphorylation consensus sequences.

Topics: Anti-HIV Agents; Carrier Proteins; Casein Kinase II; Catechin; Cell Line; Chamomile; Chromatography, Affinity; Flavonoids; Hesperidin; HIV-1; HL-60 Cells; Humans; Kinetics; NF-kappa B; Oils, Volatile; Plants, Medicinal; Protein Serine-Threonine Kinases; Recombinant Proteins; Thiophenes; Transcription, Genetic; Virus Integration; Virus Replication