guanosine-triphosphate and baicalein

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in the world. Inhibitor of differentiation 1 (Id1) is overexpressed in NSCLC and involved in promoting its progression and metastasis. Identifying natural compounds targeting Id1 may have utility in NSCLC treatment. Here, we sought to determine whether the anti-tumor activities of

Topics: A549 Cells; alpha7 Nicotinic Acetylcholine Receptor; Animals; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Flavanones; Flavonoids; Guanosine Triphosphate; Humans; Inhibitor of Differentiation Protein 1; Lung Neoplasms; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Neoplasm Metastasis; Phenotype; Phosphorylation; Plant Extracts; Scutellaria; Shelterin Complex; Telomere-Binding Proteins

Platelet-activating factor (PAF), added to the bathing solution, stimulated the cardiac muscarinic K+ channel (KACh) in the cell-attached patch (no agonist in the pipette). The PAF-induced KACh channel activation was blocked by WEB2086, a PAF-receptor inhibitor, indicating that the PAF-receptor mediated the response. PAF-induced activation was prevented by nordihydroguaieretic acid, a lipoxygenase inhibitor, and AA-861, a 5-lipoxygenase inhibitor, but was not affected by indomethacin, a cyclo-oxygenase inhibitor. The PAF-induced KACh channel activity disappeared upon formation of inside-out patch. In this inside-out patch, intracellular GTP alone induced maximal channel reactivation, which was inhibited by GDP-beta S. These results suggest that 5-lipoxygenase metabolites of PAF-released arachidonic acid cause a persistent stimulation of GK but not the KACh channel itself, resulting in a receptor-independent activation of the KACh channel by GTP.

Topics: Animals; Arachidonic Acids; Benzoquinones; Cells, Cultured; Flavanones; Flavonoids; GTP-Binding Proteins; Guanosine 5'-O-(3-Thiotriphosphate); Guanosine Triphosphate; Guinea Pigs; Heart; Heart Atria; Indomethacin; Lipoxygenase Inhibitors; Masoprocol; Membrane Potentials; Myocardium; Platelet Activating Factor; Potassium Channels; Virulence Factors, Bordetella