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.
Mol Cell Biochem. 2010 Dec;345(1-2):29-34. doi: 10.1007/s11010-010-0556-9. Epub 2010 Aug 6.
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.
单萜化合物紫苏醇（POH）是一种用于治疗多种恶性肿瘤的药物，包括神经胶质瘤。本研究定义了 POH 对豚鼠肾和脑提取物以及人神经胶质瘤细胞系中 Na/K-ATP 酶活性的抑制作用。这种抑制对肾脏酶表现出高度的选择性，与表达α（1）亚基的神经胶质瘤细胞相似。用纯化酶进行的动力学研究表明，POH 对 Na（+）和 K（+）的抑制呈非竞争性，对 ATP 的抑制呈竞争性。此外，这种药物对这些纯化制剂中钾激活的对硝基苯磷酸酶活性没有抑制作用，这表明与经典抑制剂哇巴因不同，该药物作用于酶的催化循环的初始阶段。我们认为 POH 的抗肿瘤作用可能与其与 Na/K-ATP 酶的结合特性有关。
