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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....
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Association for Dental Sciences of the Republic of China
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10316490/ https://www.ncbi.nlm.nih.gov/pubmed/37404653 http://dx.doi.org/10.1016/j.jds.2023.02.013 |
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author | Wang, Jue-Long Jan, Chung-Ren Chen, Min-Huey |
author_facet | Wang, Jue-Long Jan, Chung-Ren Chen, Min-Huey |
author_sort | Wang, Jue-Long |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10316490 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Association for Dental Sciences of the Republic of China |
record_format | MEDLINE/PubMed |
spelling | pubmed-103164902023-07-04 Action of econazole on Ca(2+) levels and cytotoxicity in OC2 human oral cancer cells Wang, Jue-Long Jan, Chung-Ren Chen, Min-Huey J Dent Sci Original Article 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. Association for Dental Sciences of the Republic of China 2023-07 2023-03-06 /pmc/articles/PMC10316490/ /pubmed/37404653 http://dx.doi.org/10.1016/j.jds.2023.02.013 Text en © 2023 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Wang, Jue-Long Jan, Chung-Ren Chen, Min-Huey Action of econazole on Ca(2+) levels and cytotoxicity in OC2 human oral cancer cells |
title | Action of econazole on Ca(2+) levels and cytotoxicity in OC2 human oral cancer cells |
title_full | Action of econazole on Ca(2+) levels and cytotoxicity in OC2 human oral cancer cells |
title_fullStr | Action of econazole on Ca(2+) levels and cytotoxicity in OC2 human oral cancer cells |
title_full_unstemmed | Action of econazole on Ca(2+) levels and cytotoxicity in OC2 human oral cancer cells |
title_short | Action of econazole on Ca(2+) levels and cytotoxicity in OC2 human oral cancer cells |
title_sort | action of econazole on ca(2+) levels and cytotoxicity in oc2 human oral cancer cells |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10316490/ https://www.ncbi.nlm.nih.gov/pubmed/37404653 http://dx.doi.org/10.1016/j.jds.2023.02.013 |
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