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Expert Opinion on Therapeutic Targets Volume 12, 2008 - Issue 11
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Review

Na+/K+-ATPase α subunits as new targets in anticancer therapy

Tatjana Mijatovic Unibioscreen SA, Brussels, Belgium
,
Laurent Ingrassia Unibioscreen SA, Brussels, Belgium
,
Vincenzo Facchini Unibioscreen SA, Brussels, Belgium
&
Robert Kiss Free University of Brussels, Institute of Pharmacy, Laboratory of Toxicology, Campus de la Plaine CP205/1, Boulevard du Triomphe, 1050 Brussels, Belgium +32 477 62 20 83; +32 23 32 53 35; [email protected]
, PhD
Pages 1403-1417 | Published online: 14 Oct 2008

Bibliography

  • Mijatovic T, Van Quaquebeke E, Delest B, et al. Cardiotonic steroids on the road to anti-cancer therapy. Biochim Biophys Acta 2007;1776:32-57
  • Skou JC. The influence of some cations on an adenosinetriphosphatase from peripheral nerves. Biochim Biophys Acta 1957;23:394-401
  • Blanco G. Na,K-ATPase subunit heterogeneity as a mechanism for tissue-specific ion regulation. Semin Nephrol 2005;25:292-303
  • Blanco G. The Na/K-ATPase and its isozymes: what we have learned using the baculovirus expression system. Front Biosci 2005;10:2397-411
  • Horisberger JD. Recent insights into the structure and mechanism of the sodium pump. Physiology (Bethesda) 2004;19:377-87
  • Lingrel JB, Kuntzweiler T. Na+,K+-ATPase. J Biol Chem 1994;269:19659-62
  • Mobasheri AJ, Avila I, Cozar-Castellano MD, et al. Na/K-ATPase isozyme diversity; comparative biochemistry and physiological implications of novel functional interactions. Biosci Rep 2000;20:51-91
  • Geering K. Function of FXYD proteins, regulators of Na, K-ATPase. J Bioenerg Biomembr 2005;37:387-92
  • Geering K. FXYD proteins: new regulators of Na-K-ATPase. Am J Physiol Renal Physiol 2006;290:F241-50
  • Blanco G, Melton RJ, Sanchez G, Mercer RW. Functional characterization of a testes-specific α subunit isoform of the Na,K-ATPase. Biochemistry 1999;38:13661-9
  • Magyar CE, Wang J, Azuma KK, McDonough AA. Reciprocal regulation of cardiac Na,K-ATPase and Na/Ca exchanger: hypertension, thyroid hormone, development. Am J Physiol Cell Physiol 1995;269:C675-82
  • Schwinger RHG, Wang J, Frank K, et al. Reduced sodium pump α1-, α3-, and β1-isoform protein levels and Na+,K+-ATPase activity but unchanged Na+–Ca2+ exchanger protein levels in human heart failure. Circulation 1999;99:2105-12
  • Espineda C, Chang JH, Twis J, et al. Repression of Na,K-ATPase β1-subunit by the transcription factor Snail in carcinoma. Mol Biol Cell 2004;15:1364-73
  • Blok LJ, Chang GT, Steenbeek-Slotboom M, et al. Regulation of expression of Na+,K+-ATPase in androgen-dependent and androgen-independent prostate cancer. Br J Cancer 1999;8:28-36
  • Akopyanz NS, Broude NE, Bekman EP, et al. Tissue-specific expression of Na,K-ATPase β-subunit. Does β2 expression correlate with tumorigenesis? FEBS Lett 1991;289:8-10
  • Boukerche H, Su ZZ, Kang DC, Fisher PB. Identification and cloning of genes displaying elevated expression as a consequence of metastatic progression in human melanoma cells by rapid subtraction hybridization. Gene 2004;343:191-201
  • Sakai H, Suzuki T, Maeda M, et al. Up-regulation of Na+,K+-ATPase α3-isoform and down-regulation of the α1-isoform in human colorectal cancer. FEBS Lett 2004;563:151-4
  • Rajasekaran SA, Ball WJ Jr, Bander NH H, et al. Reduced expression of beta-subunit of Na,K-ATPase in human clear-cell renal cell carcinoma. J Urol 1999;162:574-80
  • Lefranc F, Mijatovic T, Kondo Y, et al. Targeting the α 1 subunit of the sodium pump to combat glioblastoma cells. Neurosurgery 2008;62:211-21
  • Mijatovic T, Roland I, Van Quaquebeke E, et al. The α1 subunit of the sodium pump could represent a novel target to combat non-small cell lung cancers. J Pathol 2007;212:170-9
  • Seligson DB, Rajasekaran SA, Yu H, et al. Na,K-adenosine triphosphatase α1-subunit predicts survival of renal clear cell carcinoma. J Urol 2008;179:338-45
  • Sznajder JI, Factor P, Ingbar DH. Invited review: lung edema clearance: role of Na+-K+-ATPase. J Appl Physiol 2002;93:1860-6
  • Ewart H, Klip A. Hormonal regulation of the Na+-K+-ATPase: mechanisms underlying rapid and sustained changes in pump activity. Am J Physiol Cell Physiol 1995;269:C295-311
  • Bertorello AM, Aperia A, Walaas SI, et al. Phosphorylation of the catalytic subunit of Na+,K+-ATPase inhibits the activity of the enzyme. Proc Natl Acad Sci USA 1991;88:11359-62
  • Bertorello AM, Katz A. Regulation of Na:K pump activity: pathways between receptors and effectors. News Physiol Sci 1995;10:253-9
  • Therien AG, Blostein R. Mechanisms of sodium pump regulation. Am J Physiol Cell Physiol 2000;279:C541-66
  • Dostanic-Larson I, Van Huysse JW, Lorenz JN, Lingrel JB. The highly conserved cardiac glycoside binding site of Na,K-ATPase plays a role in blood pressure regulation. Proc Natl Acad Sci USA 2005;102:15845-50
  • Dostanic-Larson I, Lorenz JN, Van Huysse JW, et al. Physiological role of the α1- and α2-isoforms of the Na+-K+-ATPase and biological significance of their cardiac glycoside binding site. Am J Physiol Regul Integr Comp Physiol 2006;290:R524-8
  • Xie Z, Askari A. Na+/K+-ATPase as a signal transducer. Eur J Biochem 2002;269:2434-9
  • Xie Z, Cai T. Na+-K+-ATPase-mediated signal transduction: from protein interaction to cellular function. Mol Interv 2003;3:157-68
  • Pierre SV, Xie Z. The Na,K-ATPase receptor complex: its organization and membership. Cell Biochem Biophys 2006;46:303-16
  • Liang M, Cai T, Tian J, Qu W, et al. Functional characterization of Src-interacting Na/K-ATPase using RNA interference assay. J Biol Chem 2006;281:19709-19
  • Liang M, Tian J, Liu L, et al. Identification of a pool of non-pumping Na/K-ATPase. J Biol Chem 2007;282:10585-93
  • Wang H, Haas M, Liang M, et al. Ouabain assembles signaling cascades through the caveolar Na+/K+-ATPase. J Biol Chem 2004;279:17250-9
  • Mijatovic T, Lefranc F, Camby I, et al. Cardenolide-related UNBS1450 compound targets the Src kinase in the Na+/K+-ATPase signalosome and exerts potent in vitro and in vivo anti-tumor activities in experimental human glioblastomas. American Association for Cancer Research (AACR) Annual Meeting; 16 April 2005 – 20; Anaheim, USA
  • Mijatovic T, De Nève N, Gailly P, et al. Nucleolus and c-Myc: potential targets of cardenolide-mediated antitumor activity. Mol Cancer Ther 2008;7:1285-96
  • Mijatovic T, Op De Beek A, Van Quaquebeke E, et al. The cardenolide UNBS1450 is able to deactivate NF-κB-mediated cytoprotective effects in human non-small-cell-lung cancer (NSCLC) cells. Mol Cancer Ther 2006;5:391-9
  • McConkey DJ, Lin Y, Nutt LK, et al. Cardiac glycosides stimulate Ca2+ increases and apoptosis in androgen-independent, metastatic human prostate adenocarcinoma cells. Cancer Res 2000;60:3807-12
  • Newman RA, Yang P, Pawlus AD, Block KI. Cardiac glycosides as novel cancer therapeutic agents. Mol Interv 2008;8:36-49
  • Newman RA, Kondo Y, Yokoyama T, et al. Autophagic cell death of human pancreatic tumor cells mediated by oleandrin, a lipid-soluble cardiac glycoside. Integr Cancer Ther 2007;6:354-64
  • Newman RA, Yang P, Hittelman WN, et al. Oleandrin-mediated oxidative stress in human melanoma cells. J Exp Ther Oncol 2006;5:167-81
  • Trevisi L, Visentin B, Cusinato F, et al. Antiapoptotic effect of ouabain on human umbilical vein endothelial cells. Biochem Biophys Res Commun 2004;321:716-21
  • Taurin S, Dulin NO, Pchejetski D, et al. c-Fos expression in ouabain-treated vascular smooth muscle cells from rat aorta: evidence for an intracellular-sodium-mediated, calcium-independent mechanism. J Physiol 2002;15:835-47
  • Mijatovic T, Mathieu V, Gaussin JF, et al. Cardenolide-induced lysosomal membrane permeabilization contributes therapeutic benefits in experimental human non-small-cell-lung cancers. Neoplasia 2006;8:402-12
  • Lin H, Juang JL, Wang PS. Involvement of Cdk5/p25 in digoxin-triggered prostate cancer cell apoptosis. J Biol Chem 2004;279:29302-7
  • Kometiani P, Liu L, Askari A. Digitalis-induced signaling by Na+/K+-ATPase in human breast cancer cells. Mol Pharmacol 2005;67:929-36
  • Aydemir-Koksoy A, Abramowitz J, Allen JC. Ouabain induced signaling and vascular smooth muscle cell proliferation. J Biol Chem 2001;276:46605-11
  • Dvela M, Rosen H, Feldmann T, et al. Diverse biological responses to different cardiotonic steroids. Pathophysiology 2007;14:159-66
  • Pierre SV, Sottejeau Y, Gourbeau JM, et al. Isoform specificity of Na-K-ATPase-mediated ouabain signaling. Am J Physiol Renal Physiol 2008;294:F859-66
  • Rajasekaran SA, Palmer LG, Quan K, et al. Na,K-ATPase β-subunit is required for epithelial polarization, suppression of invasion, and cell motility. Mol Biol Cell 2001;12:279-95
  • Rajasekaran AK, Rajasekaran SA. Role of Na-K-ATPase in the assembly of tight junctions. Am J Physiol Renal Physiol 2003;285:F388-96
  • Rajasekaran SA, Barwe SP, Rajasekaran AK. Multiple functions of Na,K-ATPase in epithelial cells. Semin Nephrol 2005;25:328-34
  • Contreras RG, Shoshani L, Flores-Maldonado C, et al. Relationship between Na+,K+-ATPase and cell attachment. J Cell Sci 1999;112:4223-32
  • Cereijido M, Shoshani L, Contreras RG. The polarized distribution of Na+, K+-ATPase and active transport across epithelia. J Membr Biol 2001;184:299-304
  • Contreras RG, Flores-Maldonado C, Lázaro A, et al. Ouabain binding to Na+,K+-ATPase relaxes cell attachment and sends a specific signal (NACos) to the nucleus. J Membr Biol 2004;198:147-58
  • Shoshani L, Contreras RG, Roldán ML, et al. The polarized expression of Na+,K+-ATPase in epithelia depends on the association between β-subunits located in neighboring cells. Mol Biol Cell 2005;16:1071-81
  • Larre I, Ponce A, Fiorentino R, et al. Contacts and cooperation between cells depend on the hormone ouabain. Proc Natl Acad Sci USA 2006;103:10911-6
  • Rajasekaran SA, Beyenbach KW, Rajasekaran AK. Interactions of tight junctions with membrane channels and transporters. Biochim Biophys Acta 2008;1778:757-69
  • Cereijido M, Contreras RG, Shoshani L, et al. Tight junction and polarity interaction in the transporting epithelial phenotype. Biochim Biophys Acta 2008;1778:770-93
  • Melero CP, Medarde M, San Feliciano A. A short review on cardiotonic steroids and their aminoguanidine analogues. Molecules 2000;5:51-81
  • Steyn PS, Van Heerden FR. Bufadienolides of plant and animal origin. Nat Prod Rep 1998;15;397-413
  • Van Quaquebeke E, Simon G, Andre A, et al. Identification of a novel cardenolide (2″-oxovorusharin) from Calotropis procera and the hemisynthesis of novel derivatives displaying potent in vitro antitumor activities and high in vivo tolerance: Structure-activity relationship analyses. J Med Chem 2005;48:849-56
  • Hamed AI, Plaza A, Balestrieri ML, et al. Cardenolide glycosides from Pergularia tomentosa and their proapoptotic activity in Kaposi's sarcoma cells. J Nat Prod 2006;69:1319-22
  • Kopp B, Krenn L, Draxler M, et al. Bufadienolides from Urginea maritima from Egypt. Phytochemistry 1996;42:513-22
  • Bagrov AY, Shapiro JI. Endogenous digitalis: pathophysiologic roles and therapeutic applications. Nat Clin Pract Nephrol 2008;4:378-92
  • Schoner W. Endogenous cardiac glycosides, a new class of steroid hormones. Eur J Biochem 2002;269:2440-8
  • Buckalew VM. Endogenous digitalis-like factors. An historical overview. Front Biosci 2005;10:2325-34
  • Nesher M, Shpolansky U, Rosen H, Lichtstein D. The digitalis-like steroid hormones: new mechanisms of action and biological significance. Life Sci 2007;80:2093-107
  • Schoner W, Scheiner-Bobis G. Endogenous and exogenous cardiac glycosides and their mechanisms of action. Am J Cardiovasc Drugs 2007;7:173-89
  • Schoner W, Scheiner-Bobis G. Endogenous cardiac glycosides: hormones using the sodium pump as signal transducer. Semin Nephrol 2005;25:343-51
  • Aronson JK. An account of the foxglove and its medical uses 1785-1985; Incorporating a facsimile of William Withering's “An account of the foxglove and some of its medical uses 1785;”. Oxford Press; 1986
  • Rahimtoola SH. Digitalis therapy for patients in clinical heart failure. Circulation 2004;109:2942-6
  • Gheorghiade M, Adams KF Jr, Colucci WS. Digoxin in the management of cardiovascular disorders. Circulation 2004;109:2959-64
  • Swarts HGP, Koenderink JB, Willems PHGM, De Pont JJHHM. The non-gastric H,K-ATPase is oligomycin-sensitive and can function as an H+,NH4+-ATPase. J Biol Chem 2005;280:33115-22
  • Cougnon M, Planelles G, Crowson MS, et al. The rat distal colon P-ATPase α subunit encodes a ouabain-sensitive H+,K+-ATPase. J Biol Chem 1996;271:7277-80
  • Haux J. Digitoxin is a potential anti-cancer agent for several types of cancer. Med Hypoth 1999;153:543-8
  • Huang YT, Chueh SC, Teng CM, Guh JH. Investigation of ouabain-induced anti-cancer effect in human androgen-independent prostate cancer PC-3 cells. Biochem Pharmacol 2004;67:727-33
  • Yeh JH, Huang WJ, Kan SF, Wang PS. Inhibitory effects of digitalis on the proliferation of androgen dependent and independent prostate cancer cells. J Urol 2001;166:1937-42
  • Yeh JH, Huang WJ, Kan SF, Wang PS. Effects of bufalin and cinobufagin on the proliferation of androgen dependent and independent prostate cancer cells. Prostate 2003;54:112-24
  • Frese S, Frese-Schaper M, Andres AC, et al. Cardiac glycosides initiate Apo2L/TRAIL-induced apoptosis in non-small cell lung cancer cells by up-regulation of death receptors 4 and 5. Cancer Res 2006;66:5867-74
  • Pathak S, Multani AS, Narayan S, et al. Anvirzel, an extract of Nerium oleander, induces cell death in human but not murine cancer cells. Anti-cancer Drugs 2000;11:455-63
  • Sreenivasan Y, Raghavendra PB, Manna SK. Oleandrin-mediated expression of Fas potentiates apoptosis in tumor cells. J Clin Immunol 2006;26:308-22
  • Mijatovic T, Lefranc F, Van Quaquebeke E, et al. UNBS1450: a new hemi-synthetic cardenolide with promising anti-cancer activity. Drug Dev Res 2007;68:164-73
  • López-Lázaro M. Digitoxin as an anti-cancer agent with selectivity for cancer cells: possible mechanisms involved. Expert Opin Ther Targets 2007;11:1043-53
  • Available from: http://dtp.nci.nih.gov/dtpstandard/cancerscreeningdata/index.jsp
  • Mijatovic T, De Nève N, Mathieu V, Kiss R. c-Myc down-regulation as a surrogate marker of cardenolide-induced anti-tumor activity. American Association for Cancer Research (AACR) Annual Meeting; 12 April 2008 – 16; San Diego, USA
  • Simpson CD, Mawji IA, Williams MA, et al. A high throughput cell-based screen identifies inhibitors of the Na+/K+ ATPase pump as sensitizers to anoikis and inhibitors of metastasis. American Association for Cancer Research (AACR) Annual Meeting; 14 April 2007 – 18; Los Angeles, USA
  • Svensson A, Azarbayjani F, Backman U, et al. Digoxin inhibits neuroblastoma tumor growth in mice. Anti -cancer Res 2005;25:207-12
  • Han KQ, Huang G, Gu W, et al. Anti-tumor activities and apoptosis-regulated mechanisms of bufalin on the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice. World J Gastroenterol 2007;13:3374-9
  • Adams KF Jr, Gheorghiade M, Uretsky BF, et al. Clinical benefits of low serum digoxin concentrations in heart failure. J Am Coll Cardiol 2002;39:946-53
  • The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997;336:525-33
  • Gao J, Wymore R, Wymore RT, et al. Isoform-specific regulation of the sodium pump by α- and β-adrenergic agonists in the guinea-pig ventricle. J Physiol 1999;516:377-83
  • Rose AM, Qazzaz HM, Zolotarjova N, et al. Sodium pump isoforms in xenotransplantation: importance of biochemical compatibility. Clin Chem 2000;46:234-41
  • Sweadner KJ, Herrera VL, Amato S, et al. Immunologic identification of Na+,K+-ATPase isoforms in myocardium. Isoform change in deoxycorticosterone acetate-salt hypertension. Circ Res 1994;74:669-78
  • Kaplan JG. Membrane cation transport and the control of proliferation of mammalian cells. Ann Rev Physiol 1978;40:19-41
  • Shen SS, Hamamoto ST, Bern HA, Steinhardt RA. Alteration of sodium transport in mouse mammary epithelium associated with neoplastic transformation. Cancer Res 1978;38:1356-61
  • Weidemann H. Na/K-ATPase, endogenous digitalis-like compounds and cancer development – a hypothesis. Front Biosci 2005;10:2165-76
  • Espineda C, Seligson DB, Ball JW Jr, et al. Analysis of the Na/K-ATPase α- and β-subunit expression profiles of bladder cancer using tissue microarrays. Cancer 2003;97:1859-68
  • Sharabani-Yosef O, Bak A, Langzam L, et al. Rat skeletal muscle in culture expresses the α1 but not the α2 protein subunit isoform of the Na+/K+ pump. J Cell Physiol 1999;180:236-44
  • Arystarkhova E, Sweadner KJ. Hormonal and neurogenic control of Na-K-ATPase and myosin isoforms in neonatal rat cardiac myocytes. Am J Physiol 1997;273:C489-99
  • Mijatovic T, Mathieu A, De Nève N, et al. Influence of tumor micro-environment on over-expression of sodium pump α1 and α3 subunits, which represent potential targets to combat colon cancer. American Association for Cancer Research (AACR) Annual Meeting; 2008 April 12 – 16; San Diego, USA
  • Mathieu V, Pirker C, Vernier M, et al. New cardenolides, binders of the sodium pump, could represent interesting chemotherapeutical agents for melanoma treatment. American Association for Cancer Research (AACR) Annual Meeting; 2008 April 12 – 16; San Diego, USA
  • Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin 2008;58:71-96
  • Sugi K, Musch MW, Field M, Chang EB. Inhibition of Na+,K+-ATPase by interferon γ down-regulates intestinal epithelial transport and barrier function. Gastroenterology 2001;120:1393-403
  • Kreydiyyeh SI, Markossian S. Tumor necrosis factor α down-regulates the Na+-K+ATPase and the Na+-K+2Cl-cotransporter in the kidney cortex and medulla. Cytokine 2006;33:138-44
  • Suzuki Y, Lu Q, Xu DZ, et al. Na+,K+-ATPase activity is inhibited in cultured intestinal epithelial cells by endotoxin or nitric oxide. Int J Mol Med 2005;15:871-7
  • Guzman NJ, Fang MZ, Tang SS, et al. Autocrine inhibition of Na+/K+-ATPase by nitric oxide in mouse proximal tubule epithelial cells. J Clin Invest 1995;95:2083-8
  • López-Lázaro M, Pastor N, Azrak SS, et al. Digitoxin inhibits the growth of cancer cell lines at concentrations commonly found in cardiac patients. J Nat Prod 2005;68:1642-5
  • Haux J, Klepp O, Spigset O, Tretli S. Digitoxin medication and cancer; case control and internal dose-response studies. BMC Cancer 2001;1:11
  • Available from: http://clinicaltrials.gov
  • Mekhail T, Kaur H, Ganapathi R, et al. Phase I trial of Anvirzel in patients with refractory solid tumors. Invest New Drugs 2006;24:423-7
  • Takara K, Takagi K, Tsujimoto M, et al. Digoxin up-regulates multidrug resistance transporter (MDR1) mRNA and simultaneously down-regulates steroid xenobiotic receptor mRNA. Biochem Biophys Res Commun 2003;306:116-20
  • Huang DM, Guh JH, Huang YT, et al. Cardiac glycosides induce resistance to tubulin-dependent anti-cancer drugs in androgen-independent human prostate cancer. J Biomed Sci 2002;9:443-52
  • Lawrence TS, Davis MA. The influence of Na+,K+-pump blockade on doxorubicin-mediated cytotoxicity and DNA strand breakage in human tumor cells. Cancer Chemother Pharmacol 1990;26:163-7
  • Ahmed Z, Deyama Y, Yoshimura Y, Suzuki K. Cisplatin sensitivity of oral squamous carcinoma cells is regulated by Na(+),K(+)-ATPase activity rather than copper-transporting P-type ATPases, ATP7A and ATP7B. Cancer Chemother Pharmacol 2008;published online 11 June 2008, doi:10.1007/s00280-008-0781-z

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