tetrathiomolybdate has been researched along with Lymphoma--Large-B-Cell--Diffuse* in 1 studies
1 other study(ies) available for tetrathiomolybdate and Lymphoma--Large-B-Cell--Diffuse
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The copper chelator ATN-224 induces caspase-independent cell death in diffuse large B cell lymphoma.
Bcl-2 and other anti-apoptotic proteins are associated with defective caspase-dependent apoptotic pathways, resulting in chemoresistance. We have previously shown that ATN-224, a copper chelator drug, induces cell death in murine thymic lymphoma cells transfected with Bcl-2. In the current study, we tested whether ATN-224 was effective in diffuse large B cell lymphoma (DLBCL) cells, which have increased anti‑apoptotic proteins through translocation or amplification. We found that nanomolar concentrations of ATN-224 induced cell death in DLBCL cells independent of Bcl-2, Bcl-xL or Mcl-1 status. ATN-224 treatment resulted in mitochondrial dysfunction, release of apoptosis-inducing factor (AIF) and induction of caspase-independent cell death. In addition, ATN-224 degraded Mcl-1 and enhanced the effect of the BH3 mimetic ABT-263. These findings indicate that ATN-224 has potential as a therapeutic for the treatment of DLBCL. Induction of caspase‑independent cell death in apoptosis‑resistant DLBCL would provide a therapeutic alternative for the treatment of refractory disease. Topics: Aniline Compounds; Apoptosis; Apoptosis Inducing Factor; Caspases; Cell Line, Tumor; Chelating Agents; Drug Resistance, Neoplasm; Drug Synergism; Gene Expression Regulation, Neoplastic; Humans; Lymphoma, Large B-Cell, Diffuse; Mitochondria; Molybdenum; Sulfonamides | 2014 |