Action of econazole on Ca(2+) levels and cytotoxicity in OC2 human oral cancer cells

BACKGROUND/PURPOSE: Econazole is an antifungal drug. Antifungal activity of econazole against non-dermatophyte molds was reported. Econazole inhibited Ca(2+) channels and stimulated cytotoxicity in lymphoma and leukemia cells. Ca(2+) cations are crucial second envoy that triggers various processes. This research was aimed to investigate action of econazole on Ca(2+) levels and cytotoxicity in OC2 human oral cancer cells. MATERIALS AND METHODS: Cytosolic Ca(2+) levels ([Ca(2+)](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. RESULTS: Econazole at 10–50 μmol/L provoked [Ca(2+)](i) raises. Forty % of 50 μml//L econazole-induced signal was diminished when external Ca(2+) was eliminated. The Ca(2+) influx provoked by econazole was suppressed by different degrees by store-induced Ca(2+) 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 Ca(2+), econazole-caused [Ca(2+)](i) raises were abolished by thapsigargin. In contrast, econazole partially suppressed the [Ca(2+)](i) raises caused by thapsigargin. U73122 fell short to change econazole-caused [Ca(2+)](i) responses. Econazole (10–70 μmol/L) elicited cytotoxicity in a dose-dependent fashion. Blockade of 50 μmol/L econazole-induced [Ca(2+)] rises with BAPTA/AM enhanced econazole-induced cytotoxicity by 72%. CONCLUSION: Econazole evoked [Ca(2+)](i) raises and provoked cytotoxicity in a concentration-dependent manner in OC2 human oral cancer cells. In Ca(2+)-containing solution, BAPTA/AM enhanced 50 μmol/L econozole-induced cytotoxicity.