In vitro antitumor activity of cromakalim in human brain tumor cells.
The effect of cromakalim, a K+ channel opener, on the growth of human brain tumor cells was investigated. Cromakalim inhibited the growth of SK-N-MC human neuroblastoma and U-373 MG human astrocytoma cell lines in a dose-dependent manner. This effect of cromakalim was significantly blocked by the co-treatment with sulfonylureas (glibenclamide or tolbutamide) which are known as specific blockers for ATP-sensitive K+ channels. In addition, cromakalim significantly inhibited agonist-induced intracellular Ca2+ mobilization in the astrocytoma cells. This inhibition induced by cromakalim was also reversed by pretreatment with glibenclamide. These results suggest that the antitumor activity of cromakalim may be due to the activation of ATP-sensitive K+ channels leading to the inhibition of the intracellular Ca2+ signalling mechanism.
Lee
Y S
YS
Department of Neurological Surgery, Loyola University Medical Center, Maywood, Ill. 60153.
Sayeed
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MM
Wurster
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RD
D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001254:Astrocytoma / Q000188:drug therapy / Q000473:pathology; D001578:Benzopyrans / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D019806:Cromakalim; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009447:Neuroblastoma / Q000188:drug therapy / Q000473:pathology; D015221:Potassium Channels / Q000187:drug effects; D011758:Pyrroles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013453:Sulfonylurea Compounds / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D013453:Sulfonylurea Compounds; D019806:Cromakalim; D002118:Calcium