The copper chelator ATN-224 induces caspase-independent cell death in diffuse large B cell lymphoma

  • Authors:
    • Kristy Lee
    • Matthew R. Hart
    • Margaret M. Briehl
    • Andrew P. Mazar
    • Margaret E. Tome
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  • Published online on: April 23, 2014     https://doi.org/10.3892/ijo.2014.2396
  • Pages: 439-447
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Abstract

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.
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July-2014
Volume 45 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Lee K, Hart MR, Briehl MM, Mazar AP and Tome ME: The copper chelator ATN-224 induces caspase-independent cell death in diffuse large B cell lymphoma. Int J Oncol 45: 439-447, 2014.
APA
Lee, K., Hart, M.R., Briehl, M.M., Mazar, A.P., & Tome, M.E. (2014). The copper chelator ATN-224 induces caspase-independent cell death in diffuse large B cell lymphoma. International Journal of Oncology, 45, 439-447. https://doi.org/10.3892/ijo.2014.2396
MLA
Lee, K., Hart, M. R., Briehl, M. M., Mazar, A. P., Tome, M. E."The copper chelator ATN-224 induces caspase-independent cell death in diffuse large B cell lymphoma". International Journal of Oncology 45.1 (2014): 439-447.
Chicago
Lee, K., Hart, M. R., Briehl, M. M., Mazar, A. P., Tome, M. E."The copper chelator ATN-224 induces caspase-independent cell death in diffuse large B cell lymphoma". International Journal of Oncology 45, no. 1 (2014): 439-447. https://doi.org/10.3892/ijo.2014.2396