Carbonic Anhydrase Inhibitor Suppresses Invasion of Renal Cancer Cells in vitro

Acidification of the extracellular milieu of malignant tumors is reported to increase the invasive behavior of cancer cells. In normal tissues, production of acid is catalyzed by carbonic anhydrases (CAs), some of which are known to be overexpressed in certain cancers. To investigate the functional...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2000-02, Vol.97 (5), p.2220-2224
Main Authors: Parkkila, Seppo, Rajaniemi, Hannu, Parkkila, Anna-Kaisa, Kivela, Jyrki, Waheed, Abdul, Pastorekova, Silvia, Pastorek, Jaromir, Sly, William S.
Format: Article
Language:English
Subjects:
acetazolamide
Acetazolamide - pharmacology
Acidification
Amides
Animals
Antineoplastic Agents - pharmacology
Biological Sciences
Cancer
Carbonic Anhydrase Inhibitors - pharmacology
Carbonic Anhydrases - biosynthesis
Cell growth
Cell lines
Cells
Cultured cells
Isoenzymes - biosynthesis
Kidney cells
Kidney Neoplasms - drug therapy
Kidney Neoplasms - pathology
Kidneys
Medical research
Mice
Neoplasm Invasiveness
Tumor Cells, Cultured
Tumors
Western blotting
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Summary:Acidification of the extracellular milieu of malignant tumors is reported to increase the invasive behavior of cancer cells. In normal tissues, production of acid is catalyzed by carbonic anhydrases (CAs), some of which are known to be overexpressed in certain cancers. To investigate the functional role of CA activity in such cancer cells, we analyzed the effect of acetazolamide, a potent CA inhibitor, on the invasive capacity of four renal carcinoma cell lines (Caki-1, Caki-2, ACHN, and A-498). We found that 10μ M acetazolamide inhibited the relative invasion rate of these cell lines between 18-74%. The Caki-2 and ACHN cell lines displayed the highest responsiveness, and their responses clearly depended on the acetazolamide concentration in the culture medium. Immunocytochemical and Western blotting results identified the presence of CA isoenzyme II in the cytoplasm of all four cell lines and CA XII on the plasma membrane in three of four cell lines. Because acetazolamide alone reduced invasiveness of these cancer cells in vitro, we conclude that the CAs overexpressed in these renal cancer cells contribute to invasiveness, at least in vitro, and suggest that CA inhibitors may also reduce invasiveness in other tumors that overexpress one or more CAs.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.040554897