chrysin and Prostatic-Neoplasms

Topics: Caspase 3; Cell Line, Tumor; Flavonoids; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Ki-67 Antigen; Male; PC-3 Cells; Poly(ADP-ribose) Polymerase Inhibitors; Prostatic Neoplasms; Proto-Oncogene Proteins c-bcl-2; Signal Transduction; Vascular Endothelial Growth Factor A

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; eIF-2 Kinase; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Eukaryotic Initiation Factor-2; Flavonoids; G1 Phase Cell Cycle Checkpoints; Heat-Shock Proteins; Humans; Lipid Peroxidation; Male; Membrane Potential, Mitochondrial; Mitogen-Activated Protein Kinases; Oxidative Stress; Phosphatidylinositol 3-Kinase; Proliferating Cell Nuclear Antigen; Prostatic Neoplasms; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Ribosomal Protein S6 Kinases; Signal Transduction; Unfolded Protein Response

Honey is a common household product with many medicinal uses described in traditional medicine. Only recently has its antioxidant properties and preventive effects against disease been highlighted. Chrysin is a natural flavone commonly found in honey that has been shown to be an antioxidant agent. In this study, we investigated the antiproliferative and apoptotic effects of honey and chrysin on cultured human prostate cancer cells.. Cells were cultured in RPMI medium and treated with different concentrations of honey and chrysin for three consecutive days. Cell viability was quantitated by the 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The percentage of apoptotic cells was determined by flow cytometry using Annexin V-fluorescein isothiocyanate.. The MTT assay revealed that both compounds had an antiproliferative effect on PC-3 cells in a dose- and time-dependent manner. The IC50 values for honey and chrysin against PC-3 cells were 2.5% and 24.5% after 48 h and 1.8% and 8.5% after 72 h, respectively. Chrysin induced apoptosis in PC-3 cells, as determined by flow cytometry.. Our results suggest that honey has anti-proliferative effects on prostate cancer cells and the effects are mainly due to chrysin. Therefore, chrysin may be a potential compound for both cancer prevention and treatment. Further in vivo investigation is needed to support the use of chrysin in cancer therapy.

Topics: Analysis of Variance; Annexin A5; Antioxidants; Apitherapy; Apoptosis; Carcinoma; Cell Line, Tumor; Cell Proliferation; Cell Survival; Flavonoids; Flow Cytometry; Humans; Male; Prostatic Neoplasms; Time Factors

The pim-1 kinase is a true oncogene that has been implicated in the development of leukemias, lymphomas, and prostate cancer, and is the target of drug development programs. We have used experimental approaches to identify a selective, cell-permeable, small-molecule inhibitor of the pim-1 kinase to foster basic and translational studies of the enzyme. We used an ELISA-based kinase assay to screen a diversity library of potential kinase inhibitors. The flavonol quercetagetin (3,3',4',5,6,7-hydroxyflavone) was identified as a moderately potent, ATP-competitive inhibitor (IC(50), 0.34 micromol/L). Resolution of the crystal structure of PIM1 in complex with quercetagetin or two other flavonoids revealed a spectrum of binding poses and hydrogen-bonding patterns in spite of strong similarity of the ligands. Quercetagetin was a highly selective inhibitor of PIM1 compared with PIM2 and seven other serine-threonine kinases. Quercetagetin was able to inhibit PIM1 activity in intact RWPE2 prostate cancer cells in a dose-dependent manner (ED(50), 5.5 micromol/L). RWPE2 cells treated with quercetagetin showed pronounced growth inhibition at inhibitor concentrations that blocked PIM1 kinase activity. Furthermore, the ability of quercetagetin to inhibit the growth of other prostate epithelial cell lines varied in proportion to their levels of PIM1 protein. Quercetagetin can function as a moderately potent and selective, cell-permeable inhibitor of the pim-1 kinase, and may be useful for proof-of-concept studies to support the development of clinically useful PIM1 inhibitors.

Topics: Chromones; Crystallography, X-Ray; Flavones; Flavonoids; Humans; Male; Phenotype; Prostatic Neoplasms; Protein Kinase Inhibitors; Protein Structure, Secondary; Proto-Oncogene Proteins c-pim-1; Sensitivity and Specificity; Substrate Specificity