title: Chlorotoxin: a helpful natural scorpion peptide to diagnose glioma and fight tumor invasion.
abstract: Chlorotoxin is a small 36 amino-acid peptide identified from the venom of the scorpion Leiurus quinquestriatus. Initially, chlorotoxin was used as a pharmacological tool to characterize chloride channels. While studying glioma-specific chloride currents, it was soon discovered that chlorotoxin possesses targeting properties towards cancer cells including glioma, melanoma, small cell lung carcinoma, neuroblastoma and medulloblastoma. The investigation of the mechanism of action of chlorotoxin has been challenging because its cell surface receptor target remains under questioning since two other receptors have been claimed besides chloride channels. Efforts on chlorotoxin-based applications focused on producing analogues helpful for glioma diagnosis, imaging and treatment. These efforts are welcome since gliomas are very aggressive brain cancers, close to impossible to cure with the current therapeutic arsenal. Among all the chlorotoxin-based strategies, the most promising one to enhance patient mean survival time appears to be the use of chlorotoxin as a targeting agent for the delivery of anti-tumor agents. Finally, the discovery of chlorotoxin has led to the screening of other scorpion venoms to identify chlorotoxin-like peptides. So far several new candidates have been identified. Only detailed research and clinical investigations will tell us if they share the same anti-tumor potential as chlorotoxin.
authors.affiliation: Grenoble Neuroscience Institute, Inserm U836, Team 3, Chemin Fortuné Ferrini, Bâtiment Edmond Safra, 38042 Grenoble Cedex 09, France. EBrambilla@chu-grenoble.fr.|Science Technology Health, Université Joseph Fourier, BP53, 38041 Grenoble, France. EBrambilla@chu-grenoble.fr.|Labex Ion Channel Science and Therapeutics, 660 route des lucioles, 06560 Valbonne, France. EBrambilla@chu-grenoble.fr.
authors.forename: Lucie
authors.initials: L
authors.lastname: Dardevet
authors.affiliation: Grenoble Neuroscience Institute, Inserm U836, Team 3, Chemin Fortuné Ferrini, Bâtiment Edmond Safra, 38042 Grenoble Cedex 09, France. EBrambilla@chu-grenoble.fr.|Science Technology Health, Université Joseph Fourier, BP53, 38041 Grenoble, France. EBrambilla@chu-grenoble.fr.
authors.forename: Dipti
authors.initials: D
authors.lastname: Rani
authors.affiliation: Grenoble Neuroscience Institute, Inserm U836, Team 3, Chemin Fortuné Ferrini, Bâtiment Edmond Safra, 38042 Grenoble Cedex 09, France. mahmoudfs2000@yahoo.com.|Science Technology Health, Université Joseph Fourier, BP53, 38041 Grenoble, France. mahmoudfs2000@yahoo.com.|Labex Ion Channel Science and Therapeutics, 660 route des lucioles, 06560 Valbonne, France. mahmoudfs2000@yahoo.com.|Zoology Department, Faculty of Science, Minia University, 61519 Minia, Egypt. mahmoudfs2000@yahoo.com.
authors.forename: Tarek Abd El
authors.initials: TA
authors.lastname: Aziz
authors.affiliation: Ecole des Mines d'Ales, 6 av de Clavieres, 30100 Ales Cedex, France. ingrid.bazin@mines-ales.fr.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Bazin
authors.affiliation: Inserm UMR 1097, 163, Avenue de Luminy, 13288 Marseille Cedex 09, France. sabatier.jm1@libertysurf.fr.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Sabatier
authors.affiliation: Zoology Department, Faculty of Science, Minia University, 61519 Minia, Egypt. mahmoudfs2000@yahoo.com.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Fadl
authors.affiliation: Science Technology Health, Université Joseph Fourier, BP53, 38041 Grenoble, France. EBrambilla@chu-grenoble.fr.|Institut Albert Bonniot, Inserm U823, Rond-Point de la Chantourne, 38706 La Tronche Cedex, France. EBrambilla@chu-grenoble.fr.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Brambilla
authors.affiliation: Grenoble Neuroscience Institute, Inserm U836, Team 3, Chemin Fortuné Ferrini, Bâtiment Edmond Safra, 38042 Grenoble Cedex 09, France. michel.dewaard@ujf-grenoble.fr.|Science Technology Health, Université Joseph Fourier, BP53, 38041 Grenoble, France. michel.dewaard@ujf-grenoble.fr.|Labex Ion Channel Science and Therapeutics, 660 route des lucioles, 06560 Valbonne, France. michel.dewaard@ujf-grenoble.fr.|Smartox Biotechnology, 570 Rue de la Chimie, Bâtiment Nanobio campus, 38400 Saint-Martin d'Hères, France. michel.dewaard@ujf-grenoble.fr.
authors.forename: Michel
authors.initials: M
authors.lastname: De Waard
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D005910:Glioma / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D009498:Neurotoxins / Q000627:therapeutic use*; D010455:Peptides / Q000627:therapeutic use; D012604:Scorpion Venoms / Q000627:therapeutic use*; D012605:Scorpions
chemical_list: D009498:Neurotoxins; D010455:Peptides; D012604:Scorpion Venoms; C091539:Chlorotoxin
references.citation: Nucleic Acids Res. 2009 Jan;37(Database issue):D387-92
references.pmid: 18931379
references.citation: J Biol Chem. 2010 Feb 12;285(7):4366-74
references.pmid: 20018898
references.citation: J Physiol. 1995 Jan;482:19S-25S
references.pmid: 7730971
references.citation: J Neurooncol. 2001 Jun;53(2):129-47
references.pmid: 11716066
references.citation: BMC Biochem. 2001;2:16
references.pmid: 11782289
references.citation: Nanomedicine (Lond). 2008 Aug;3(4):495-505
references.pmid: 18694312
references.citation: Neuropathol Appl Neurobiol. 2006 Jun;32(3):271-7
references.pmid: 16640645
references.citation: Comp Biochem Physiol A Mol Integr Physiol. 1998 Dec;121(4):323-32
references.pmid: 10048185
references.citation: Bioinformatics. 2006 Jan 15;22(2):195-201
references.pmid: 16301204
references.citation: Anticancer Res. 2000 Nov-Dec;20(6B):4227-33
references.pmid: 11205252
references.citation: Small. 2008 Mar;4(3):372-9
references.pmid: 18232053
references.citation: Curr Pharm Des. 2007;13(35):3568-75
references.pmid: 18220793
references.citation: Front Biosci (Landmark Ed). 2014;19:818-24
references.pmid: 24389226
references.citation: Pflugers Arch. 2000 Oct;440(6):881-8
references.pmid: 11041554
references.citation: J Pept Res. 1997 Jun;49(6):545-55
references.pmid: 9266482
references.citation: J Nucl Med. 2005 Apr;46(4):580-6
references.pmid: 15809479
references.citation: FEBS Lett. 1998 Dec 28;441(3):387-91
references.pmid: 9891977
references.citation: Am J Physiol. 1997 Oct;273(4 Pt 1):C1290-7
references.pmid: 9357773
references.citation: J Clin Oncol. 2006 Aug 1;24(22):3644-50
references.pmid: 16877732
references.citation: Nucleic Acids Res. 2004 Jan 1;32(Database issue):D230-4
references.pmid: 14681401
references.citation: Toxicon. 2000 May;38(5):661-8
references.pmid: 10673158
references.citation: J Neurooncol. 2005 May;73(1):1-7
references.pmid: 15933810
references.citation: Glia. 2002 Aug;39(2):162-73
references.pmid: 12112367
references.citation: J Biol Chem. 2009 Sep 18;284(38):26051-62
references.pmid: 19574231
references.citation: Int J Pharm. 2012 Jan 17;422(1-2):264-70
references.pmid: 22101282
references.citation: J Control Release. 2011 Jun 30;152(3):402-10
references.pmid: 21435361
references.citation: J Neurosci. 1999 Jul 15;19(14):5942-54
references.pmid: 10407033
references.citation: J Inorg Biochem. 2012 May;110:58-63
references.pmid: 22465700
references.citation: Nucleic Acids Res. 2014 Jul;42(Web Server issue):W252-8
references.pmid: 24782522
references.citation: J Biol Chem. 2007 Dec 28;282(52):37545-55
references.pmid: 17951250
references.citation: Nano Lett. 2005 Jun;5(6):1003-8
references.pmid: 15943433
references.citation: Philos Trans R Soc Lond B Biol Sci. 2014 Mar 19;369(1638):20130095
references.pmid: 24493743
references.citation: Peptides. 2011 Apr;32(4):656-63
references.pmid: 21262299
references.citation: Cancer Res. 1998 Nov 1;58(21):4871-9
references.pmid: 9809993
references.citation: J Med Chem. 2011 Feb 10;54(3):782-7
references.pmid: 21210710
references.citation: Biotechnol Lett. 2011 Jul;33(7):1309-17
references.pmid: 21424168
references.citation: J Neurooncol. 2012 May;107(3):457-62
references.pmid: 22108716
references.citation: Toxicon. 2002 Sep;40(9):1239-58
references.pmid: 12220709
references.citation: Biotechnol Lett. 2006 Sep;28(18):1439-43
references.pmid: 16791718
references.citation: Biomaterials. 2009 Feb;30(4):649-57
references.pmid: 18990439
references.citation: Acta Pharmacol Sin. 2007 Dec;28(12):2019-26
references.pmid: 18031618
references.citation: Toxicon. 1991;29(11):1403-8
references.pmid: 1726031
references.citation: J Cell Biochem. 2000 Jul 19;79(1):28-37
references.pmid: 10906753
references.citation: Am J Physiol. 1993 Feb;264(2 Pt 1):C361-9
references.pmid: 8383429
references.citation: Expert Opin Drug Deliv. 2007 Mar;4(2):175-86
references.pmid: 17335414
references.citation: J Biol Chem. 2003 Feb 7;278(6):4135-44
references.pmid: 12454020
references.citation: Nature. 2004 Nov 18;432(7015):396-401
references.pmid: 15549107
references.citation: ACS Nano. 2010 Aug 24;4(8):4587-94
references.pmid: 20731441
references.citation: Nucleic Acids Res. 2009 Jul;37(Web Server issue):W485-91
references.pmid: 19443448
references.citation: Nanomedicine. 2011 Dec;7(6):744-52
references.pmid: 21419873
references.citation: Biomaterials. 2011 Aug;32(22):5177-86
references.pmid: 21531455
references.citation: Biotechnol Lett. 2005 Oct;27(20):1597-603
references.pmid: 16245180
references.citation: Cancer Res. 2009 Aug 1;69(15):6200-7
references.pmid: 19638572
references.citation: Small. 2009 Feb;5(2):256-64
references.pmid: 19089837
references.citation: Exp Biol Med (Maywood). 2008 Jul;233(7):779-91
references.pmid: 18445774
references.citation: J Neurooncol. 2005 Jan;71(2):113-9
references.pmid: 15690125
references.citation: Neuron Glia Biol. 2006 Feb;2(1):39-49
references.pmid: 16520829
references.citation: Anticancer Res. 2010 Nov;30(11):4515-24
references.pmid: 21115901
references.citation: Cancer Res. 2007 Jul 15;67(14):6882-8
references.pmid: 17638899
references.citation: Biotechnol Bioeng. 2013 Apr;110(4):1211-20
references.pmid: 23125026
references.citation: Toxicon. 2000 Aug;38(8):1009-14
references.pmid: 10708793
references.citation: Chin J Cancer. 2010 Jun;29(6):626-30
references.pmid: 20507737
references.citation: Curr Pharm Des. 2011 Dec;17(38):4362-71
references.pmid: 22204434
references.citation: Neurosci Lett. 2007 Jan 22;412(1):62-7
references.pmid: 17166663
references.citation: J Drug Deliv. 2012;2012:975763
references.pmid: 23304519
references.citation: Adv Drug Deliv Rev. 2011 Jul 18;63(8):582-96
references.pmid: 21295093
references.citation: J Neurosci. 2011 Oct 5;31(40):14346-60
references.pmid: 21976520
references.citation: Biomaterials. 2010 Nov;31(31):8032-42
references.pmid: 20673683
references.citation: Electrophoresis. 2009 Jun;30 Suppl 1:S162-73
references.pmid: 19517507
references.citation: Neuroscience. 1998 Apr;83(4):1161-73
references.pmid: 9502255
references.citation: Biomaterials. 2011 Mar;32(9):2399-406
references.pmid: 21185076
references.citation: Anticancer Res. 2010 Jan;30(1):39-46
references.pmid: 20150615
references.citation: Biochem Biophys Res Commun. 2007 Oct 19;362(2):225-9
references.pmid: 17707767
references.citation: J Neurosci. 2003 Jul 2;23(13):5572-82
references.pmid: 12843258