Action of econazole on Ca 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 channels and stimulated cytotoxicity in lymphoma and leukemia cells. Ca cations are crucial second envoy that triggers various processes. This research was aimed to investigate action of econazole on Ca levels and cytotoxicity in OC2 human oral cancer cells.

MATERIALS AND METHODS

Cytosolic Ca levels ([Ca]) 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] raises. Forty % of 50 μml//L econazole-induced signal was diminished when external Ca was eliminated. The Ca influx provoked by econazole was suppressed by different degrees by store-induced Ca 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, econazole-caused [Ca] raises were abolished by thapsigargin. In contrast, econazole partially suppressed the [Ca] raises caused by thapsigargin. U73122 fell short to change econazole-caused [Ca] responses. Econazole (10-70 μmol/L) elicited cytotoxicity in a dose-dependent fashion. Blockade of 50 μmol/L econazole-induced [Ca] rises with BAPTA/AM enhanced econazole-induced cytotoxicity by 72%.

CONCLUSION

Econazole evoked [Ca] raises and provoked cytotoxicity in a concentration-dependent manner in OC2 human oral cancer cells. In Ca-containing solution, BAPTA/AM enhanced 50 μmol/L econozole-induced cytotoxicity.