maitotoxin and Breast-Neoplasms

Treatment of MCF-7 breast cancer cells with the marine toxin maitotoxin (MTX) induces cell death. The cytotoxic effects are clearly detectable within 2-4 h after cell treatment with 10(-10)-10(-9) M concentrations of MTX. The response was found to depend on extracellular Ca2+, inasmuch as cell death was prevented when culture dishes received MTX, following addition of EGTA. MTX caused transient phosphorylation of extracellular signal-regulated kinase isoforms 1 and 2 (ERK1 and ERK2) mitogen-activated protein kinase isoforms in MCF-7 cells, which was maximal 15 min after toxin addition to culture vessels. The effect was dependent on influx of extracellular Ca2+, as it was abolished by EGTA, and was induced by ionophores, such as A23187 and ionomycin. Our findings show that signaling pathways involving Ca2+ ions may cause activation of ERK1 and ERK2 in cell death responses.

Topics: Breast Neoplasms; Calcium; Calcium-Calmodulin-Dependent Protein Kinases; Dose-Response Relationship, Drug; Egtazic Acid; Enzyme Activation; Extracellular Space; Humans; Marine Toxins; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; Oxocins; Phosphorylation; Tumor Cells, Cultured