Carbonic Anhydrase Inhibitor Suppresses Invasion of Renal Cancer Cells in vitro

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 97; no. 5; pp. 2220 - 2224
• Main Authors: Parkkila, Seppo, Rajaniemi, Hannu, Parkkila, Anna-Kaisa, Kivela, Jyrki, Waheed, Abdul, Pastorekova, Silvia, Pastorek, Jaromir, Sly, William S.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 29-02-2000; National Academy of Sciences; The National Academy of Sciences
• 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
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.040554897

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.