Τίτλος:
Effects of modulation of the NO/cGMP pathway in tumor cell lines derived from the upper airway tract
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Nitric oxide (NO) is known to be expressed in a variety of cell types and exert its effects through autocrine and paracrine mechanisms. To characterize the NO/cGMP pathway in tumor cells of the upper airway tract, we studied the cell lines Detroit 562, FaDu and FAT7. Using isoform-specifi c antibodies, we were unable to detect expression of NO synthases in the above-mentioned cells lines. To evaluate whether tumor cells respond to NO, we exposed cells to the NO donor sodium nitroprusside (SNP). Stimulation of Detroit 562 and FaDu with SNP (10 μgrave; mol/l to 1 mmol/l) led to a concentrationdependent increase in cGMP accumulation. In addition, incubation of cells with SNP, but not 8 Br-cGMP, reduced Detroit 562 cell number. As exposure of cells to SNP decreased 3H-thymidine incorporation without inducing DNA fragmentation, we attributed the observed decrease in cell number to inhibition of cell proliferation rather than induction of apoptosis. On the other hand, exposure of Detroit 562 to high concentrations of SNP (1 mmol/l) led to apoptosis and increased the release of vascular endothelial growth factor. We conclude that, although human cell lines derived from the upper airway tract do not produce NO, they respond to NO released by neighboring cells and that exposure to NO exerts an anti- proliferative/apoptotic effect that is independent of cGMP generation. Copyright © 2004 S. Karger AG, Basel.
Συγγραφείς:
Papapetropoulos, N.
Zhou, Z.
Roussos, C.
Goumas, P.
Papapetropoulos, A.
Περιοδικό:
Clinical Pharmacology Onhand
Λέξεις-κλειδιά:
8 bromoguanosine phosphate; cyclic GMP; DNA fragment; enzyme antibody; nitric oxide; nitric oxide synthase; nitroprusside sodium; thymidine; tritium; vasculotropin, apoptosis; article; cell count; cell proliferation; concentration response; controlled study; drug effect; drug exposure; human; human cell; human tissue; priority journal; protein expression; protein secretion; respiratory tract tumor; signal transduction; tumor cell; upper respiratory tract, Animals; Apoptosis; Caspase 3; Caspases; Cell Count; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cyclic GMP; Enzyme Inhibitors; Guanylate Cyclase; Humans; Nitric Oxide; Nitric Oxide Donors; Nitric Oxide Synthase; Rats; Receptors, Cytoplasmic and Nuclear; Respiratory System; Vascular Endothelial Growth Factor A
