anticancer drug perillyl alcohol is a Na/K-ATPase inhibitor

• Published in: Molecular and cellular biochemistry 2010-12, Vol.345 (1-2), p.29-34
• Main Authors: Garcia, Diogo G, Amorim, Lidia M. F, de Castro Faria, Mauro V, Freire, Aline S, Santelli, Ricardo E, Da Fonseca, Clóvis O, Quirico-Santos, Thereza, Burth, Patricia
• Format: Article
• Language: English
• Subjects: A172 glioma cells; Adenosine triphosphatase; Animals; Antimitotic agents; Antineoplastic Agents; ATP; Biochemistry; Biomedical and Life Sciences; Brain - enzymology; Cardiology; Catalysis; Cell Line, Tumor; Cells; Drug therapy; Enzyme Inhibitors; Glioblastoma - enzymology; Guinea Pigs; Humans; Inhibitor drugs; Kidney - enzymology; Kidneys; Kinetics; Life Sciences; Medical Biochemistry; Monoterpenes - pharmacology; Na/K-ATPase; Oncology; Ouabain; Perillyl alcohol; Protein Binding; Sodium-Potassium-Exchanging ATPase - antagonists & inhibitors; Toy industry; Tumors
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-010-0556-9

The monoterpene perillyl alcohol (POH) is a drug used in the treatment of several malignant tumors, including gliomas. The present study defines a POH inhibitory effect on Na/K-ATPase activity from kidney and brain guinea pig extracts and from a human glioblastoma cell line. This inhibition showed a high degree of selectivity toward the kidney enzyme expressing, as do glioblastoma cells, the α₁ subunit. Kinetic studies with purified enzymes showed a noncompetitive POH inhibition profile to Na⁺ and K⁺ and an uncompetitive inhibition towards ATP. Furthermore, potassium activated p-nitrophenylphosfatase activity of these purified preparations was not inhibited by POH, suggesting that this drug, differently from the classical inhibitor ouabain, acted in the initial phase of the enzyme's catalytic cycle. We suggest that POH antitumor action could be linked to its Na/K-ATPase binding properties.