Action of econazole on Ca2+ levels and cytotoxicity in OC2 human oral cancer cells.

Econazole is an antifungal drug. Antifungal activity of econazole against non-dermatophyte molds was reported. Econazole inhibited Ca²⁺ channels and stimulated cytotoxicity in lymphoma and leukemia cells. Ca²⁺ cations are crucial second envoy that triggers various processes. This research was aimed to investigate action of econazole on Ca²⁺ levels and cytotoxicity in OC2 human oral cancer cells. Cytosolic Ca²⁺ levels ([Ca²⁺] i) were detected employing fura-2 as a probe in a RF-5301PC spectrofluorophotometer (Shimadzu). Cytotoxicity was determined using 4-[3-[4-lodophenyl]-2-4(4-nitrophenyl)-2H-5-tetrazolio-1,3-benzene disulfonate] (WST-1) to detect fluorescence changes. Econazole at 10–50 μmol/L provoked [Ca²⁺] i raises. Forty % of 50 μml//L econazole-induced signal was diminished when external Ca²⁺ was eliminated. The Ca²⁺ influx provoked by econazole was suppressed by different degrees by store-induced Ca²⁺ influx suppressors SKF96365 and nifedipine; GF109203X (a protein C [PKC] inhibitor); an extracellular signaling pathway (ERK) 1/2 blocker PD98059, and phospholipase A2 suppressor aristolochic acid, but was enhanced by phorbol 12-myristate 13 acetate (PMA; a PKC activator) by 18%. Without external Ca²⁺, econazole-caused [Ca²⁺] i raises were abolished by thapsigargin. In contrast, econazole partially suppressed the [Ca²⁺] i raises caused by thapsigargin. U73122 fell short to change econazole-caused [Ca²⁺] i responses. Econazole (10–70 μmol/L) elicited cytotoxicity in a dose-dependent fashion. Blockade of 50 μmol/L econazole-induced [Ca²⁺] rises with BAPTA/AM enhanced econazole-induced cytotoxicity by 72%. Econazole evoked [Ca²⁺] i raises and provoked cytotoxicity in a concentration-dependent manner in OC2 human oral cancer cells. In Ca²⁺-containing solution, BAPTA/AM enhanced 50 μmol/L econozole-induced cytotoxicity. [ABSTRACT FROM AUTHOR]