@Article{096504017X14965111926391,
AUTHOR = {Anne Riemann, Antje Güttler, Verena Haupt, Henri Wichmann, Sarah Reime, Matthias Bache, Dirk Vordermark, Oliver Thews},
TITLE = {Inhibition of Carbonic Anhydrase IX by Ureidosulfonamide Inhibitor  U104 Reduces Prostate Cancer Cell Growth, But Does Not Modulate  Daunorubicin or Cisplatin Cytotoxicity},
JOURNAL = {Oncology Research},
VOLUME = {26},
YEAR = {2018},
NUMBER = {2},
PAGES = {191--200},
URL = {http://www.techscience.com/or/v26n2/56630},
ISSN = {1555-3906},
ABSTRACT = {Carbonic anhydrase (CA) IX has emerged as a promising target for cancer therapy. It is highly upregulated in 
hypoxic regions and mediates pH regulation critical for tumor cell survival as well as extracellular acidification of the tumor microenvironment, which promotes tumor aggressiveness via various mechanisms, such as 
augmenting metastatic potential. Therefore, the aim of this study was to analyze the complex interdependency 
between CA IX and the tumor microenvironment in prostate tumor cells with regard to potential therapeutic 
implications. CA IX was upregulated by hypoxia as well as acidosis in prostate cancer cells. This induction did 
not modulate intracellular pH but led to extracellular acidification. Pharmacological inhibition of CA IX activity by U104 (SLC-0111) resulted in a reduction in tumor cell growth and an increase in apoptotic cell death. 
Intracellular pH was reduced under normoxic and even more so under hypoxic conditions when CA IX level 
was high. However, although intracellular pH regulation was disturbed, targeting CA IX in combination with 
daunorubicin or cisplatin did not intensify apoptotic tumor cell death. Hence, targeting CA IX in prostate cancer cells can lead to intracellular pH dysregulation and, consequently, can reduce cellular growth and elevate 
apoptotic cell death. Attenuation of extracellular acidification by blocking CA IX might additionally impede 
tumor progression and metastasis. However, no beneficial effect was seen when targeting CA IX in combination with chemotherapeutic drugs.},
DOI = {10.3727/096504017X14965111926391}
}