This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Chang, H-T Articles by Jan, C-R Search for Related Content PubMed PubMed Citation Articles by Chang, H-T Articles by Jan, C-R Social Bookmarking                   What's this?

Econazole induces increases in free intracellular Ca2+ concentrations in human osteosarcoma cells

Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

C-S Liu

Department of Surgery, Ping Tung Christian Hospital, Ping Tung, Taiwan

C-T Chou

Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

C-H Hsieh

C-H Chang

W-C Chen

Department of Surgery, Ping Tung Christian Hospital, Ping Tung, Taiwan

S-I Liu

S-S Hsu

J-S Chen

B-P Jiann

J-K Huang

Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

C-R Jan

Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwancrjan{at}isca.vghks.gov.tw

Econazole is an antifungal drug with different in vitro effects. However, econazole's effect on osteoblast like cells is unknown. In human MG63 osteosarcoma cells, the effect of econazole on intracellular Ca²⁺ concentrations ([Ca²⁺]_i) was explored by using fura-2. At a concentration of 0.1 µM, econazole started to cause a rise in [Ca²⁺]_i in a concentration-dependent manner. Econazole-induced [Ca²⁺]_i rise was reduced by 74% by removal of extracellular Ca²⁺. The econazole-induced Ca²⁺ influx was mediated via a nimodipine-sensitive pathway. In Ca²⁺ free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca²⁺ ATPase, caused a [Ca²⁺]_i rise, after which the increasing effect of econazole on [Ca²⁺]_i was abolished. Pretreatment of cells with econazole to deplete Ca²⁺ stores totally prevented thapsigargin from releasing Ca²⁺. U73122, an inhibitor of phospholipase C, abolished histamine (an inositol 1,4,5-trisphosphate dependent Ca²⁺ mobilizer)-induced, but not econazoleinduced, [Ca²⁺]_i rise. Econazole inhibited 76% of thapsigargin-induced store-operated Ca²⁺ entry. These findings suggest that in MG63 osteosarcoma cells, econazole increases [Ca²⁺]_i by stimulating Ca²⁺ influx and Ca²⁺ release from the endoplasmic reticulum via a phospholipase C-independent manner. In contrast, econazole acts as a potent blocker of store-operated Ca²⁺ entry.

Key Words: Ca2+ • Ca2+ stores • econazole • fura-2 • human MG63 osteosarcoma cells

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?