title: Effect of m-3m3FBS on Ca2+ handling and viability in OC2 human oral cancer cells.
abstract: The effect of 2,4,6-trimethyl-N-(meta-3-trifluoromethyl-phenyl)-benzenesulfonamide (m-3M3FBS), a presumed phospholipase C activator, on cytosolic free Ca2+ concentrations ([Ca2+]i) in OC2 human oral cancer cells is unclear. This study explored whether m-3M3FBS changed basal [Ca2+]i levels in suspended OC2 cells by using fura-2 as a Ca2+-sensitive fluorescent dye. M-3M3FBS at concentrations between 10-60 μM increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced partly by removing extracellular Ca2+. M-3M3FBS-induced Ca2+ influx was inhibited by the store-operated Ca2+ channel blockers nifedipine, econazole and SK&F96365, and by the phospholipase A2 inhibitor aristolochic acid. In Ca2+-free medium, 30 μM m-3M3FBS pretreatment inhibited the [Ca2+]i rise induced by the endoplasmic reticulum Ca2+ pump inhibitors thapsigargin and 2,5-di-tert-butylhydroquinone (BHQ). Conversely, pretreatment with thapsigargin, BHQ or cyclopiazonic acid partly reduced m-3M3FBS-induced [Ca2+]i rise. Inhibition of inositol 1,4,5-trisphosphate formation with U73122 did not alter m-3M3FBS-induced [Ca2+]i rise. At concentrations between 5 and 100 μM m-3M3FBS killed cells in a concentration-dependent manner. The cytotoxic effect of m-3M3FBS was not reversed by prechelating cytosolic Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Propidium iodide staining data suggest that m-3M3FBS (20 or 50 μM) induced apoptosis in a Ca2+-independent manner. Collectively, in OC2 cells, m-3M3FBS induced [Ca2+]i rise by causing inositol 1,4,5-trisphosphate-independent Ca2+ release from the endoplasmic reticulum and Ca2+ influx via phospholipase A2-sensitive store-operated Ca2+ channels. M-3M3FBS also induced Ca2+-independent cell death and apoptosis.
authors.affiliation: Kaohsiung Veterans General Hospital Department of Otolaryngology Kaohsiung Taiwan.
authors.forename: Chao-Chuan
authors.initials: CC
authors.lastname: Chi
authors.forename: Chiang-Ting
authors.initials: CT
authors.lastname: Chou
authors.forename: Chun-Chi
authors.initials: CC
authors.lastname: Kuo
authors.forename: Yao-Dung
authors.initials: YD
authors.lastname: Hsieh
authors.forename: Wei-Zhe
authors.initials: WZ
authors.lastname: Liang
authors.forename: Li-Ling
authors.initials: LL
authors.lastname: Tseng
authors.forename: Hsing-Hao
authors.initials: HH
authors.lastname: Su
authors.forename: Sau-Tung
authors.initials: ST
authors.lastname: Chu
authors.forename: Chin-Man
authors.initials: CM
authors.lastname: Ho
authors.forename: Chung-Ren
authors.initials: CR
authors.lastname: Jan
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D004963:Estrenes / Q000494:pharmacology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology*; D000096926:Benzenesulfonamides
chemical_list: D002118:Calcium; D004963:Estrenes; D015544:Inositol 1,4,5-Trisphosphate; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D013449:Sulfonamides; C473783:2,4,6-trimethyl-N-(meta-3-trifluoromethylphenyl)benzenesulfonamide; D000096926:Benzenesulfonamides; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione