Pharmacological inhibition of carbonic anhydrase XII interferes with cell proliferation and induces cell apoptosis in T-cell lymphomas

Cancer Lett. 2013 Jun 1;333(1):76-88. doi: 10.1016/j.canlet.2013.01.020. Epub 2013 Jan 21.

Abstract

The membrane-bound carbonic anhydrase isoforms CAIX and CAXII, underpin a pH-regulating system that enables hypoxic tumor cell survival. Here, we observed for the first time an upregulation of CAXII in T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LL) cells. First we showed that CAXII is overexpressed in thymocytes from tPTEN-/- mice suffering of T lymphoma and that its pharmacological inhibition decreased cell proliferation and induced apoptosis. The same results were observed with the SupT1 human T cell lymphoma line. In addition we observed an upregulation of CAXII in human T-ALL samples supporting the case that CAXII may represent a new therapeutic target for T-ALL/LL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Carbonic Anhydrases / drug effects
  • Carbonic Anhydrases / genetics
  • Carbonic Anhydrases / physiology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Humans
  • Hydrogen-Ion Concentration
  • Lymphoma, T-Cell / drug therapy*
  • Lymphoma, T-Cell / enzymology
  • Mice
  • PTEN Phosphohydrolase / physiology

Substances

  • Carbonic Anhydrase Inhibitors
  • PTEN Phosphohydrolase
  • Pten protein, mouse
  • Carbonic Anhydrases
  • carbonic anhydrase XII