title: Effects of econazole on Ca2+ levels in and the growth of human prostate cancer PC3 cells.
abstract: 1. Econazole is used clinically as an antifungal drug with many different in vitro effects. However, the effects of econazole on prostate cancer cells are unknown. The effects of econazole on intracellular Ca2+ concentrations ([Ca2+]i) in and the proliferation of human PC3 prostate cancer cells was explored in the present study using fura-2 and tetrazolium as fluorescent dyes. 2. At a concentration of 0.1 micromol/L, econazole started to increase [Ca2+]i in a concentration-dependent manner. The econazole-induced increase in [Ca2+]i was reduced by 48% by removal of extracellular Ca2+, suggesting that the econazole-induced increase in [Ca2+]i was composed of extracellular Ca2+ influx and intracellular Ca2+. 3. This econazole-induced Ca2+ influx was via an L-type Ca2+ channel-like pathway. In Ca2+-free medium, 1 micromol/L thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+-ATPase, caused a monophasic increase in [Ca2+]i, after which the effect of econazole to increase [Ca2+]i was substantially inhibited. Conversely, pretreatment with 5 micromol/L econazole to deplete intracellular Ca2+ stores totally prevented thapsigargin from releasing more Ca2+. 4. The phospholipase C (PLC) inhibitor U73122 (2 micromol/L) abolished the increase in [Ca2+]i induced by 10 micromol/L ATP (a Ca2+ mobilizer that needs inositol 1,4,5-trisphosphate). 5. Overnight incubation with 1-30 micromol/L econazole inhibited proliferation of PC3 cells in a concentration-dependent manner. 6. These findings suggest that, in PC3 cells, econazole increases [Ca2+]i by stimulating Ca2+ influx into cells and Ca2+ release from the endoplasmic reticulum via a PLC-independent mechanism. Econazole is cytotoxic at submicromolar concentrations.
authors.affiliation: Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, Republic of China.
authors.forename: Jong-Khing
authors.initials: JK
authors.lastname: Huang
authors.forename: Chung-Shin
authors.initials: CS
authors.lastname: Liu
authors.forename: Chiang-Ting
authors.initials: CT
authors.lastname: Chou
authors.forename: Shiuh-Inn
authors.initials: SI
authors.lastname: Liu
authors.forename: Shu-Shong
authors.initials: SS
authors.lastname: Hsu
authors.forename: Hong-Tai
authors.initials: HT
authors.lastname: Chang
authors.forename: Ching-Hong
authors.initials: CH
authors.lastname: Hsieh
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Chang
authors.forename: Wei-Chuan
authors.initials: WC
authors.lastname: Chen
authors.forename: Chung-Ren
authors.initials: CR
authors.lastname: Jan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects; D020013:Calcium Signaling / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004464:Econazole / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D013997:Time Factors; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D020746:Calcium Channels, L-Type; D004464:Econazole; D010738:Type C Phospholipases