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

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Abstract

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.

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Acknowledgments

This work was supported by grants from Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ), Brazil; Conselho Nacional de Pesquisas (CNPq) and Programa de Fomento à Pesquisa na Universidade Federal Fluminense (FOPESQ-UFF). The main authors and collaborators declare that have no potential conflicts of interest including patent applications/registrations and grants.

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Authors and Affiliations

  1. Departamento de Biologia Celular e Molecular, Instituto de Biologia, Universidade Federal Fluminense, Outeiro de São João Batista, s/n°, Centro, Niterói, RJ, 24020-141, Brazil

    Diogo G. Garcia, Lidia M. F. Amorim, Thereza Quirico-Santos & Patricia Burth

  2. Departamento de Medicina Interna, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil

    Mauro V. de Castro Faria

  3. Departamento de Geoquímica, Instituto de Química, Universidade Federal Fluminense, Niterói, RJ, Brazil

    Aline S. Freire & Ricardo E. Santelli

  4. Departamento de Cirurgia, Faculdade de Medicina, Hospital Antonio Pedro, Universidade Federal Fluminense, Niterói, RJ, Brazil

    Clóvis O. Da Fonseca

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  1. Diogo G. Garcia
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  2. Lidia M. F. Amorim
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Correspondence to Patricia Burth.

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Garcia, D.G., Amorim, L.M.F., de Castro Faria, M.V. et al. The anticancer drug perillyl alcohol is a Na/K-ATPase inhibitor. Mol Cell Biochem 345, 29–34 (2010). https://doi.org/10.1007/s11010-010-0556-9

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  • DOI: https://doi.org/10.1007/s11010-010-0556-9

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