calpain and cupric-chloride

Triple-negative breast cancers (TNBC) often exhibit an aggressive phenotype. Disulfiram (DSF) is an approved drug for the treatment of alcohol dependence, but has also been shown to kill TNBC cells in a copper (Cu)-dependent manner. Exactly how this occurs has not been clearly elucidated. We sought to investigate the mechanisms responsible for DSF/Cu-dependent induction of apoptosis and suppression of lung colonization by TNBC cells. DSF/Cu induced anoikis and significantly suppressed cell migration and invasion with negative effects on focal adhesions, coinciding with vimentin breakdown and calpain activation in TNBC cells. In a xenograft tumor model, DSF suppressed tumor growth and lung nodule growth, which was also associated with calpain activation. These findings warrant further investigation of disulfiram as a potential treatment for metastatic TNBC.

Topics: Animals; Anoikis; Antineoplastic Agents; Calpain; Cell Line, Tumor; Cell Movement; Cell Proliferation; Copper; Cytoskeleton; Disulfiram; Dose-Response Relationship, Drug; Enzyme Activation; Female; Focal Adhesions; Humans; Lung Neoplasms; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Proteolysis; Signal Transduction; Time Factors; Triple Negative Breast Neoplasms; Tumor Burden; Vimentin; Xenograft Model Antitumor Assays

The heart rate and calpain activity of blue mussels Mytilus edulis from the sublittoral zone, exposed to different levels of water-borne copper and cadmium, was investigated in a long-term experiment. The content of cadmium and copper in the blue mussel was determined using flame and graphite Atomic absorption spectroscopy. The observed concentrations ranged from 2.5 to 89.1 μg/g dry weight for cadmium and from 6.1 to 51.0 μg/g dry weight for copper in the control and highest concentration, respectively. Initially, increase in cardiac activity in response to copper and Cadmium exposure was observed under all pollutant concentrations (5-250 and 10-500 μg/L, respectively). The calpain-like activity in gills and hepatopancreas of the mussels treated with metals changed in dose- and time-dependent manner: from a sharp rise at the 250 μg/L concentration of copper on the first day to a significant decrease under the effect of Cadmium in the concentration of 500 μg/L on the third day of the experiment. These results suggest that: (i) heart rate oscillation may reflect active adaptation of blue mussels to contamination and (ii) animals have different sensitivity to copper and Cadmium according to the role of the metals in the mussels' life activity.

Topics: Animals; Arctic Regions; Biomarkers; Cadmium; Cadmium Chloride; Calpain; Copper; Dose-Response Relationship, Drug; Environmental Monitoring; Gills; Heart Rate; Hepatopancreas; Myocardium; Mytilus edulis; Russia; Water Pollutants, Chemical