title: Na/K-ATPase mimetic pNaKtide peptide inhibits the growth of human cancer cells.
abstract: 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.
authors.affiliation: Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, Ohio 43614, USA.
authors.forename: Zhichuan
authors.initials: Z
authors.lastname: Li
authors.forename: Zhongbing
authors.initials: Z
authors.lastname: Zhang
authors.forename: Joe X
authors.initials: JX
authors.lastname: Xie
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Jiang
authors.initials: J
authors.lastname: Tian
authors.forename: Ting
authors.initials: T
authors.lastname: Cai
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Cui
authors.forename: Hanfei
authors.initials: H
authors.lastname: Ding
authors.forename: Joseph I
authors.initials: JI
authors.lastname: Shapiro
authors.forename: Zijian
authors.initials: Z
authors.lastname: Xie
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D000254:Sodium-Potassium-Exchanging ATPase; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D010455:Peptides; D016392:Proto-Oncogene Proteins pp60(c-src); D000254:Sodium-Potassium-Exchanging ATPase