Pharmacological inhibition of carbonic anhydrase XII interferes with cell proliferation and induces cell apoptosis in T-cell lymphomas.
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.
INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Team 4, Inflammation, Cancer, Cellules Souches Cancéreuses, Nice, France.
Nadia
N
Lounnas
Célia
C
Rosilio
Marielle
M
Nebout
Didier
D
Mary
Emmanuel
E
Griessinger
Zouhour
Z
Neffati
Johanna
J
Chiche
Hergen
H
Spits
Thijs J
TJ
Hagenbeek
Vahid
V
Asnafi
Sally-Ann
SA
Poulsen
Claudiu T
CT
Supuran
Jean-François
JF
Peyron
Véronique
V
Imbert
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016399:Lymphoma, T-Cell / Q000188:drug therapy* / Q000201:enzymology; D051379:Mice; D051059:PTEN Phosphohydrolase / Q000502:physiology
D002257:Carbonic Anhydrase Inhibitors; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; D002256:Carbonic Anhydrases; C477378:carbonic anhydrase XII