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Oleandrin

Oleandrin is a lipid soluble cardiac glycoside with potential antineoplastic activity. Upon administration, oleandrin specifically binds to and inhibits the alpha3 subunit of the Na/K-ATPase pump in human cancer cells. This may inhibit the phosphorylation of Akt, upregulate MAPK, inhibit NF-kb activation and inhibit FGF-2 export and may downregulate mTOR thereby inhibiting p70S6K and S6 protein expression. All of this may lead to an induction of apoptosis. As cancer cells with relatively higher expression of the alpha3 subunit and with limited expression of the alpha1 subunit are more sensitive to oleandrin, one may predict the tumor response to treatment with lipid-soluble cardiac glycosides such as oleandrin based on the tumors Na/K-ATPase pump protein subunit expression. Overexpression of the alpha3 subunit in tumor cells correlates with tumor proliferation. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)

Oleandrin is also a toxic cardiac glycoside found in oleander (Nerium oleander L.). Along with neandrin it is primarily responsible for the toxicity of the sap of oleander. Oleandrin has been used for many years in China and Russia for its properties as a cardiac glycoside, for both suicidal and therapeutic purposes as in treatment of cardiac insufficiency.

Application: Detection in biological specimens

Oleander extracts have been used as an instrument for both suicidal and homicidal poisonings. Oleandrin, the primary active constituent, may be quantified in serum, whole blood or urine to confirm a diagnosis of poisoning in hospitalized patients or to assist in the forensic investigation of a case of fatal overdosage. Most commercial immunoassays for digoxin or digitoxin will cross-react with the oleander glycosides and will suffice for clinical monitoring purposes, but forensic scientists generally rely on instrumental techniques such as liquid chromatography-mass spectrometry (Source: http://en.wikipedia.org/wiki/Oleandrin).  

Current developer:    Phoenix Biotechnology

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2: Lin Y, Ho DH, Newman RA. Human tumor cell sensitivity to oleandrin is dependent on relative expression of Na+, K+ -ATPase subunitst. J Exp Ther Oncol. 2010;8(4):271-86. PubMed PMID: 21222360.

3: Yang P, Menter DG, Cartwright C, Chan D, Dixon S, Suraokar M, Mendoza G, Llansa N, Newman RA. Oleandrin-mediated inhibition of human tumor cell proliferation: importance of Na,K-ATPase alpha subunits as drug targets. Mol Cancer Ther. 2009 Aug;8(8):2319-28. Epub 2009 Aug 11. PubMed PMID: 19671733.

4: Lin Y, Dubinsky WP, Ho DH, Felix E, Newman RA. Determinants of human and mouse melanoma cell sensitivities to oleandrin. J Exp Ther Oncol. 2008;7(3):195-205. PubMed PMID: 19066128.

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6: Newman RA, Kondo Y, Yokoyama T, Dixon S, Cartwright C, Chan D, Johansen M, Yang P. Autophagic cell death of human pancreatic tumor cells mediated by oleandrin, a lipid-soluble cardiac glycoside. Integr Cancer Ther. 2007 Dec;6(4):354-64. PubMed PMID: 18048883.

7: Dasgupta A, White D. Stability of oleander extract and oleandrin in sera stored in plastic serum separator tubes. Ann Clin Biochem. 2007 Sep;44(Pt 5):485-7. PubMed PMID: 17761037.

8: Poindexter BJ, Feng W, Dasgupta A, Bick RJ. Oleandrin produces changes in intracellular calcium levels in isolated cardiomyocytes: a real-time fluorescence imaging study comparing adult to neonatal cardiomyocytes. J Toxicol Environ Health A. 2007 Mar 15;70(6):568-74. PubMed PMID: 17365610.

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10: Raghavendra PB, Sreenivasan Y, Manna SK. Oleandrin induces apoptosis in human, but not in murine cells: dephosphorylation of Akt, expression of FasL, and alteration of membrane fluidity. Mol Immunol. 2007 Mar;44(9):2292-302. Epub 2006 Dec 14. PubMed PMID: 17173971.

11: Gechtman C, Guidugli F, Marocchi A, Masarin A, Zoppi F. Unexpectedly dangerous escargot stew: oleandrin poisoning through the alimentary chain. J Anal Toxicol. 2006 Nov-Dec;30(9):683-6. PubMed PMID: 17137529.

12: Emanuele E, Olivieri V, Aldeghi A, Minoretti P. Topical administration of oleandrin could protect against gentamicin ototoxicity via inhibition of activator protein-1 and c-Jun N-terminal kinase. Med Hypotheses. 2007;68(3):711. Epub 2006 Oct 20. PubMed PMID: 17055668.

13: Sreenivasan Y, Raghavendra PB, Manna SK. Oleandrin-mediated expression of Fas potentiates apoptosis in tumor cells. J Clin Immunol. 2006 Jul;26(4):308-22. Epub 2006 Jun 16. PubMed PMID: 16779680.

14: Newman RA, Yang P, Hittelman WN, Lu T, Ho DH, Ni D, Chan D, Vijjeswarapu M, Cartwright C, Dixon S, Felix E, Addington C. Oleandrin-mediated oxidative stress in human melanoma cells. J Exp Ther Oncol. 2006;5(3):167-81. PubMed PMID: 16528968.

15: Tor ER, Filigenzi MS, Puschner B. Determination of oleandrin in tissues and biological fluids by liquid chromatography-electrospray tandem mass spectrometry. J Agric Food Chem. 2005 Jun 1;53(11):4322-5. PubMed PMID: 15913289.

16: Tiwari S, Singh A. Toxic and sub-lethal effects of oleandrin on biochemical parameters of fresh water air breathing murrel, Channa punctatus (Bloch.). Indian J Exp Biol. 2004 Apr;42(4):413-8. PubMed PMID: 15088692.

17: Afaq F, Saleem M, Aziz MH, Mukhtar H. Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion markers in CD-1 mouse skin by oleandrin. Toxicol Appl Pharmacol. 2004 Mar 15;195(3):361-9. PubMed PMID: 15020199.

18: Sreenivasan Y, Sarkar A, Manna SK. Oleandrin suppresses activation of nuclear transcription factor-kappa B and activator protein-1 and potentiates apoptosis induced by ceramide. Biochem Pharmacol. 2003 Dec 1;66(11):2223-39. PubMed PMID: 14609747.

19: Dasgupta A, Cao S, Wells A. Activated charcoal is effective but equilibrium dialysis is ineffective in removing oleander leaf extract and oleandrin from human serum: monitoring the effect by measuring apparent digoxin concentration. Ther Drug Monit. 2003 Jun;25(3):323-30. PubMed PMID: 12766561.

20: Hamad K, Iwamoto A, Miyazaki S, Yamanaka N, Guruge KS. Determination of bovine blood oleandrin by high-performance liquid chromatography and postcolumn derivatization. J Chromatogr Sci. 2002 Oct;40(9):515-8. PubMed PMID: 12433114.

21: Ni D, Madden TL, Johansen M, Felix E, Ho DH, Newman RA. Murine pharmacokinetics and metabolism of oleandrin, a cytotoxic component of Nerium oleander. J Exp Ther Oncol. 2002 Sep-Oct;2(5):278-85. PubMed PMID: 12416031.

22: Nasu S, Milas L, Kawabe S, Raju U, Newman R. Enhancement of radiotherapy by oleandrin is a caspase-3 dependent process. Cancer Lett. 2002 Nov 28;185(2):145-51. PubMed PMID: 12169388.

23: Smith JA, Madden T, Vijjeswarapu M, Newman RA. Inhibition of export of fibroblast growth factor-2 (FGF-2) from the prostate cancer cell lines PC3 and DU145 by Anvirzel and its cardiac glycoside component, oleandrin. Biochem Pharmacol. 2001 Aug 15;62(4):469-72. PubMed PMID: 11448457.

24: Manna SK, Sah NK, Newman RA, Cisneros A, Aggarwal BB. Oleandrin suppresses activation of nuclear transcription factor-kappaB, activator protein-1, and c-Jun NH2-terminal kinase. Cancer Res. 2000 Jul 15;60(14):3838-47. PubMed PMID: 10919658.

25: Dasgupta A, Emerson L. Neutralization of cardiac toxins oleandrin, oleandrigenin, bufalin, and cinobufotalin by digibind: monitoring the effect by measuring free digitoxin concentrations. Life Sci. 1998;63(9):781-8. PubMed PMID: 9740315.

26: Namera A, Yashiki M, Okada K, Iwasaki Y, Kojima T. Rapid quantitative analysis of oleandrin in human blood by high-performance liquid chromatography. Nihon Hoigaku Zasshi. 1997 Aug;51(4):315-8. PubMed PMID: 9366138.

27: Datta P, Dasgupta A. Interference of oleandrin and oleandrigenin in digitoxin immunoassays: minimal cross reactivity with a new monoclonal chemiluminescent assay and high cross reactivity with the fluorescence polarization assay. Ther Drug Monit. 1997 Aug;19(4):465-9. PubMed PMID: 9263390.

28: Jortani SA, Helm RA, Valdes R Jr. Inhibition of Na,K-ATPase by oleandrin and oleandrigenin, and their detection by digoxin immunoassays. Clin Chem. 1996 Oct;42(10):1654-8. PubMed PMID: 8855150.

29: Rule G, McLaughlin LG, Henion J. A quest for oleandrin in decayed human tissue. Anal Chem. 1993 Oct 1;65(19):857A-863A. PubMed PMID: 8238947.

30: Blum LM, Rieders F. Oleandrin distribution in a fatality from rectal and oral Nerium oleander extract administration. J Anal Toxicol. 1987 Sep-Oct;11(5):219-21. PubMed PMID: 3682781.

31: Deavers SI, Rosborough JP, Hoff HE, McCrady JD. Effects of oleandrin on cardiovascular hemodynamics in the dog. Am J Vet Res. 1979 Oct;40(10):1421-5. PubMed PMID: 575023.

32: Deavers S, Rosborough JP, McCrady JD. The effects of oleandrin on cardiac contractility in the normal dog. Arch Int Pharmacodyn Ther. 1979 Jun;239(2):283-95. PubMed PMID: 573605.

33: Vlasenko LM, Rubtsov AF. [Extraction of digitoxin, oleandrin and lanatoside C with organic solvents]. Farmatsiia. 1972 Sep-Oct;21(5):46-7. Russian. PubMed PMID: 4676971.

34: Vlasenko LM. [Forensic chemical analysis of decomposed cadaveric material for oleandrin]. Sud Med Ekspert. 1969 Jul-Sep;12(3):27-9. Russian. PubMed PMID: 5382587.

35: Storz H. [On the effect of the oleander glycoside Corrigen (Oleandrin). Clinical studies]. Med Welt. 1967 Jul 15;28:1650-5. German. PubMed PMID: 5629364.

36: Burton LE, Picchioni AL, Chin L. Dipotassium edetate as an antidote in poisoning from oleander and its chief glycoside, oleandrin. Arch Int Pharmacodyn Ther. 1965 Nov;158(1):202-11. PubMed PMID: 4955020.

37: YEAU KL, WHONG H, WONG CK. [THE PHARMACOLOGY OF OLEANDRIN COMPARED WITH G-STROPHANTHIN, DIGOXIN AND DIGITOXIN]. Yao Xue Xue Bao. 1965 Mar;12:180-4. Chinese. PubMed PMID: 14316669.

38: LI CT, DENG SH, HO GB. [COMPARISON OF CARDIOTONIC ACTIONS BETWEEN OLEANDRIN AND DIGITOXIN]. Yao Xue Xue Bao. 1964 Aug;11:540-4. Chinese. PubMed PMID: 14206165.

39: FAZZINI G. [OLEANDRIN ASSOCIATED WITH A CORONARY DILATOR IN THE TREATMENT OF CARDIAC INSUFFICIENCY]. Riforma Med. 1963 Aug 10;77:876-80. Italian. PubMed PMID: 14084884.

40: MARTELLI A. [Results of the use of oleandrin in therapy of myocardial insufficiency; review and personal experience]. Minerva Med. 1954 Mar 10;45(20):690-4. Undetermined Language. PubMed PMID: 13165225.

41: WOLFRED MM. The evaluation of the glycoside oleandrin, on the embryo chick heart. J Am Pharm Assoc Am Pharm Assoc. 1949 Nov;38(11):581-4. PubMed PMID: 15392528.