title: NPC-15199, a novel anti-inflammatory agent, mobilizes intracellular Ca2+ in bladder female transitional carcinoma (BFTC) cells.
abstract: This report demonstrates that NPC-15199 [(N-(9-fluorenylmethoxycarbonyl)L-leucine)], a novel anti-inflammatory agent, increases intracellular Ca2+ concentration ([Ca2+]i) in human bladder female transitional cancer (BFTC) cells. Using fura-2 as a Ca2+ probe, NPC-15199 (0.1-2 mM) was found to increase [Ca2+]i concentration-dependently. The response saturated at 2-5 mM NPC-15199. The [Ca2+]i increase comprised an initial rise, a slow decay, and a plateau. Ca2+ removal partly inhibited the Ca2+ signals. In Ca2+-free medium, pretreatment with 1 mM NPC-15199 abolished the [Ca2+]i increase induced by 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor); and after pretreatment with thapsigargin, NPC-15199-induced Ca2+ release was dramatically inhibited. This indicates that NPC-15199 released internal Ca2+ mostly from the endoplasmic reticulum. Adding 3 mM Ca2+ increased [Ca2+]i in cells pretreated with 1 mM NPC-15199 in Ca2+-free medium. Together, the findings suggest that in BFTC bladder cancer cells, NPC-15199 induced Ca2+ release from the endoplasmic reticulum and activating Ca2+ entry.
authors.affiliation: Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Taiwan, ROC. crjan@isca.vghks.gov.tw
authors.forename: C R
authors.initials: CR
authors.lastname: Jan
authors.forename: C C
authors.initials: CC
authors.lastname: Yu
authors.forename: J K
authors.initials: JK
authors.lastname: Huang
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism*; D005260:Female; D005449:Fluorenes / Q000494:pharmacology*; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005449:Fluorenes; C082231:N-(fluorenyl-9-methoxycarbonyl)leucine; D007930:Leucine; D002118:Calcium