Nitric oxide inhibits irreversibly P815 cell proliferation: involvement of potassium channels.
Nitric oxide (NO) has been shown to inhibit both normal and cancer cell proliferation. Potassium channels are involved in cell proliferation and, as NO activates these channels, we investigated the effect of NO on the proliferation of murine mastocytoma cell lines and the putative involvement of potassium channels. NO (in the form of NO donors) caused dose-dependent inhibition of cell proliferation in the P815 cell line inducing growth arrest in the mitosis phase. Incubation with NO donor for 4 or 24 h had a similar inhibitory effect on cell proliferation, indicating that this effect is irreversible. The inhibitory effect of NO was completely prevented by the blockade of voltage- and calcium-dependent potassium channels, but not by blockade of ATP-dependent channels. NO inhibition of cell proliferation was unaffected by guanylate cyclase and by cytoskeleton disruptors. Therefore, NO inhibits cell proliferation irreversibly via a potassium channel-dependent but guanylate cyclase-independent pathway in murine mastocytoma cells.
Costa
R S A
RS
Department of Pharmacology, Center of Biological Sciences, Universidade Federal de Santa Catarina, Brazil.
Assreuy
J
J
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002452:Cell Count / Q000379:methods; D002455:Cell Division / Q000187:drug effects; D004396:Coloring Agents; D003599:Cytoskeleton / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005840:Gentian Violet; D006131:Growth Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D007700:Kinetics; D034801:Mastocytoma / Q000188:drug therapy* / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004396:Coloring Agents; D004791:Enzyme Inhibitors; D006131:Growth Inhibitors; D020030:Nitric Oxide Donors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C110881:S-nitro-N-acetylpenicillamine; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D006162:Guanylate Cyclase; D010396:Penicillamine; D005840:Gentian Violet