title: Effect of calmidazolium on Ca(+2) movement and proliferation in human osteosarcoma cells.
abstract: In human MG63 osteosarcoma cells, the effect of calmidazolium on [Ca(2+)](i) and proliferation was explored using fura-2 and ELISA, respectively. Calmidazolium, at concentrations greater than 0.1 micromol/L, caused a rapid increase in [Ca(2+)](i) in a concentration-dependent manner (EC(50) = 0.5 micromol/L). The calmidazolium-induced [Ca(2+)](i) increase was reduced by 66% by removal of extracellular Ca(2+). In Ca(2+)-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca(2+)-ATPase, caused a monophasic increase in [Ca(2+)](i), after which the effect of calmidazolium to increase [Ca(2+)](i) was completely inhibited. U73122, an inhibitor of phospholipase C (PLC), abolished histamine (but not calmidazolium)-induced increases in [Ca(2+)](i). Pretreatment with phorbol 12-myristate 13-acetate to activate protein kinase C inhibited the calmidazolium-induced increase in [Ca(2+)](i) in Ca(2+)-containing medium by 47%. Separately, it was found that overnight treatment with 2-10 micromol/L calmidazolium inhibited cell proliferation in a concentration-dependent manner. These results suggest that calmidazolium increases [Ca(2+)](i) by stimulating extracellular Ca(2+) influx and also by causing release of intracellular Ca(2+) from the endoplasmic reticulum in a PLC-independent manner. Calmidazolium may be cytotoxic to osteosarcoma cells.
authors.affiliation: Department of Dentistry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Li-Lin
authors.initials: LL
authors.lastname: Tseng
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Huang
authors.forename: Shu-Shong
authors.initials: SS
authors.lastname: Hsu
authors.forename: Jin-Shyr
authors.initials: JS
authors.lastname: Chen
authors.forename: He-Hsiung
authors.initials: HH
authors.lastname: Cheng
authors.forename: Hong-Tai
authors.initials: HT
authors.lastname: Chang
authors.forename: Bang-Ping
authors.initials: BP
authors.lastname: Jiann
authors.forename: Chung-Ren
authors.initials: CR
authors.lastname: Jan
mesh_terms: D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005456:Fluorescent Dyes; D016257:Fura-2; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007700:Kinetics; D010006:Osteoblasts / Q000187:drug effects; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology*; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D007093:Imidazoles; C031938:calmidazolium; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D002118:Calcium; D016257:Fura-2