title: Modulation of intracellular calcium homeostasis by trimethyltin chloride in human tumour cells: neuroblastoma SY5Y and cervix adenocarcinoma HeLa S3.
abstract: Physiological modifications of intracellular Ca2+ ([Ca2+]i) levels trigger and/or regulate a diversity of cellular activities (e.g. neurotransmitter release, synaptic plasticity, muscular contraction, cell proliferation), while calcium overloads could result in cytotoxicity. Previously, we have shown that trimethyltin chloride (Me3SnCl; TMT) modulates calcium homeostasis in cervix adenocarcinoma (HeLa S3) cells [Florea, A.-M., Dopp, E., Büsselberg, D., 2005. TMT induces elevated calcium transients in HeLa cells: types and levels of response. Cell Calcium 37, 252-258]. Here we compare [Ca2+]i-changes induced by trimethyltin chloride in neuroblastoma SY5Y and HeLa S3 cells using calcium-sensitive dyes (fluo-4/AM (fluo-4) and rhod-2/AM (rhod-2)) and laser scanning microscopy (LSM). TMT-induced calcium elevations in neuroblastoma SY5Y as well as in HeLa S3 cells. [Ca2+]i rose to a sustained plateau or to transient spikes. Overall, the detected averaged increase of the maximum calcium elevation were: 0.5 microM approximately 125.6%; 5 microM approximately 130.1%; 500 microM approximately 145% in HeLa S3 cells and 0.5 microM approximately 133.3%; 5 microM approximately 136.1%; 500 microM approximately 147.1% in neuroblastoma SY5Y cells. The calcium rise derived from internal stores did not significantly depend on the presence of calcium in the external solution: approximately 109% (no calcium added) versus approximately 117% (2 mM calcium; 5 microM TMT) in HeLa cells. This difference was similar in neuroblastoma SY5Y cells, were approximately 127% versus approximately 136% increase (5 microM TMT) were measured. Staining of calcium stores with rhod-2 showed a TMT-induced [Ca2+]i-decrease in the stores followed by an increase of the calcium concentration in the nuclei of the two cell lines tested. Our results suggest that toxic effects in human tumour cells after exposure to trimethyltin compounds might be due to an elevation of [Ca2+]i.
authors.affiliation: Institute of Hygiene and Occupational Medicine, University Hospital Essen, Germany.
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Florea
authors.forename: Frank
authors.initials: F
authors.lastname: Splettstoesser
authors.forename: Elke
authors.initials: E
authors.lastname: Dopp
authors.forename: Albert W
authors.initials: AW
authors.lastname: Rettenmeier
authors.forename: Dietrich
authors.initials: D
authors.lastname: Büsselberg
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism*; D018613:Microscopy, Confocal; D009447:Neuroblastoma / Q000378:metabolism; D014298:Trimethyltin Compounds / Q000633:toxicity*
chemical_list: D005456:Fluorescent Dyes; D014298:Trimethyltin Compounds; C046488:trimethyltin; D002118:Calcium