The anticancer drug perillyl alcohol is a Na/K-ATPase inhibitor.
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 α(1) 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.
Garcia
Diogo G
DG
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.
Amorim
Lidia M F
LM
de Castro Faria
Mauro V
MV
Freire
Aline S
AS
Santelli
Ricardo E
RE
Da Fonseca
Clóvis O
CO
Quirico-Santos
Thereza
T
Burth
Patricia
P
D000818:Animals; D000970:Antineoplastic Agents; D001921:Brain / Q000201:enzymology; D002384:Catalysis; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors; D005909:Glioblastoma / Q000201:enzymology; D006168:Guinea Pigs; D006801:Humans; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D039821:Monoterpenes / Q000494:pharmacology*; D011485:Protein Binding; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D039821:Monoterpenes; C032208:perillyl alcohol; D000254:Sodium-Potassium-Exchanging ATPase