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J Biol Chem. 2011 Sep 16;286(37):32394-403. doi: 10.1074/jbc.M110.207597. Epub 2011 Jul 22.

Na/K-ATPase mimetic pNaKtide peptide inhibits the growth of human cancer cells.

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Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, Ohio 43614, USA.


Cells contain a large pool of nonpumping Na/K-ATPase that participates in signal transduction. Here, we show that the expression of α1 Na/K-ATPase is significantly reduced in human prostate carcinoma as well as in several human cancer cell lines. This down-regulation impairs the ability of Na/K-ATPase to regulate Src-related signaling processes. A supplement of pNaKtide, a peptide derived from α1 Na/K-ATPase, reduces the activities of Src and Src effectors. Consequently, these treatments stimulate apoptosis and inhibit growth in cultures of human cancer cells. Moreover, administration of pNaKtide inhibits angiogenesis and growth of tumor xenograft. Thus, the new findings demonstrate the in vivo effectiveness of pNaKtide and suggest that the defect in Na/K-ATPase-mediated signal transduction may be targeted for developing new anticancer therapeutics.

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