{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:12:27Z","timestamp":1790244747274,"version":"4.1.0"},"reference-count":31,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2017,10,27]],"date-time":"2017-10-27T00:00:00Z","timestamp":1509062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Spider venoms constitute incredibly diverse libraries of compounds, many of which are involved in prey capture and defence. Polyamines are often prevalent in the venom and target ionotropic glutamate receptors. Here we show that a novel spider polyamine, PA366, containing a hydroxyphenyl-based structure is present in the venom of several species of tarantula, and has selective toxicity against MCF-7 breast cancer cells. By contrast, a polyamine from an Australian funnel-web spider venom, which contains an identical polyamine tail to PA366 but an indole-based head-group, is only cytotoxic at high concentrations. Our results suggest that the ring structure plays a role in the cytotoxicity and that modification to the polyamine head group might lead to more potent and selective compounds with potential as novel cancer treatments.<\/jats:p>","DOI":"10.3390\/toxins9110346","type":"journal-article","created":{"date-parts":[[2017,10,27]],"date-time":"2017-10-27T11:33:28Z","timestamp":1509104008000},"page":"346","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["The Aromatic Head Group of Spider Toxin Polyamines Influences Toxicity to Cancer Cells"],"prefix":"10.3390","volume":"9","author":[{"given":"David","family":"Wilson","sequence":"first","affiliation":[{"name":"Centre for Biodiscovery and Molecular Development of Therapeutics, AITHM, James Cook University, Cairns, QLD 4878, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1385-529X","authenticated-orcid":false,"given":"Glen","family":"Boyle","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lachlan","family":"McIntyre","sequence":"additional","affiliation":[{"name":"Centre for Tropical Environmental and Sustainable Sciences, James Cook University, Cairns, QLD 4878, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5353-7712","authenticated-orcid":false,"given":"Matthew","family":"Nolan","sequence":"additional","affiliation":[{"name":"Centre for Biodiscovery and Molecular Development of Therapeutics, AITHM, James Cook University, Cairns, QLD 4878, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0473-3346","authenticated-orcid":false,"given":"Peter","family":"Parsons","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Smith","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon","family":"Tribolet","sequence":"additional","affiliation":[{"name":"Centre for Biodiscovery and Molecular Development of Therapeutics, AITHM, James Cook University, Cairns, QLD 4878, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Loukas","sequence":"additional","affiliation":[{"name":"Centre for Biodiscovery and Molecular Development of Therapeutics, AITHM, James Cook University, Cairns, QLD 4878, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Liddell","sequence":"additional","affiliation":[{"name":"Centre for Tropical Environmental and Sustainable Sciences, James Cook University, Cairns, QLD 4878, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3616-0279","authenticated-orcid":false,"given":"Lachlan","family":"Rash","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia"},{"name":"School of Biomedical Sciences, University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norelle","family":"Daly","sequence":"additional","affiliation":[{"name":"Centre for Biodiscovery and Molecular Development of Therapeutics, AITHM, James Cook University, Cairns, QLD 4878, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,10,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9753","DOI":"10.1073\/pnas.1107020108","article-title":"2D NMR-spectroscopic screening reveals polyketides in ladybugs","volume":"108","author":"Deyrup","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.semcancer.2016.03.005","article-title":"Cancer prevention and therapy through the modulation of transcription factors by bioactive natural compounds","volume":"40\u201341","author":"Shanmugam","year":"2016","journal-title":"Semin. Cancer Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1038\/nchembio.1659","article-title":"A roadmap for natural product discovery based on large-scale genomics and metabolomics","volume":"10","author":"Doroghazi","year":"2014","journal-title":"Nat. Chem. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"661","DOI":"10.4155\/fmc.12.4","article-title":"Ion channel drug discovery: Challenges and future directions","volume":"4","author":"Wickenden","year":"2012","journal-title":"Future Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.toxicon.2006.01.018","article-title":"Venom landscapes: Mining the complexity of spider venoms via a combined cdna and mass spectrometric approach","volume":"47","author":"Escoubas","year":"2006","journal-title":"Toxicon"},{"key":"ref_6","unstructured":"(2017, April 10). World Spider Catalog v18.0. Available online: http:\/\/www.wsc.nmbe.ch\/."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.3390\/toxins2122851","article-title":"Spider-venom peptides as therapeutics","volume":"2","author":"Saez","year":"2010","journal-title":"Toxins (Basel)"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"14283","DOI":"10.1073\/pnas.0806840105","article-title":"NMR-spectroscopic screening of spider venom reveals sulfated nucleosides as major components for the brown recluse and related species","volume":"105","author":"Schroeder","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.pharmthera.2007.01.009","article-title":"Neurotoxins from invertebrates as anticonvulsants: From basic research to therapeutic application","volume":"114","author":"Mortari","year":"2007","journal-title":"Pharmacol. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1111\/j.1582-4934.2007.00077.x","article-title":"Physiological polyamines: Simple primordial stress molecules","volume":"11","author":"Rhee","year":"2007","journal-title":"J. Cell. Mol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.3892\/ijo.2014.2597","article-title":"Pharmacological and dietary agents for colorectal cancer chemoprevention: Effects on polyamine metabolism (review)","volume":"45","author":"Linsalata","year":"2014","journal-title":"Int. J. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.toxicon.2004.11.013","article-title":"Polyamine toxins: Development of selective ligands for ionotropic receptors","volume":"45","author":"Stromgaard","year":"2005","journal-title":"Toxicon"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"374079","DOI":"10.1155\/2014\/374079","article-title":"Natural product polyamines that inhibit human carbonic anhydrases","volume":"2014","author":"Davis","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8621","DOI":"10.1093\/nar\/gku539","article-title":"Conjugation with polyamines enhances the antibacterial and anticancer activity of chloramphenicol","volume":"42","author":"Kostopoulou","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0006-291X(90)91431-Q","article-title":"Structures of paralytic acylpolyamines from the spider agelenopsis aperta","volume":"169","author":"Quistad","year":"1990","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1124\/pr.109.002451","article-title":"Glutamate receptor ion channels: Structure, regulation, and function","volume":"62","author":"Traynelis","year":"2010","journal-title":"Pharmacol. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/j.toxicon.2006.01.014","article-title":"Taxonomy of australian funnel-web spiders using rp-hplc\/esi-ms profiling techniques","volume":"47","author":"Wilson","year":"2006","journal-title":"Toxicon"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1255\/ejms.1213","article-title":"A template approach for the characterization of linear polyamines and derivatives in spider venom","volume":"19","author":"Tzouros","year":"2013","journal-title":"Eur. J. Mass Spectrom. (Chichester)"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/0041-0101(90)90298-L","article-title":"Chemical characterization of acylpolyamine toxins from venom of a trap-door spider and two tarantulas","volume":"28","author":"Skinner","year":"1990","journal-title":"Toxicon"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.4155\/fmc.14.103","article-title":"Spider venomics: Implications for drug discovery","volume":"6","author":"Pineda","year":"2014","journal-title":"Future Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.gene.2013.06.064","article-title":"Regulation of cell proliferation and migration in gallbladder cancer by zinc finger x-chromosomal protein","volume":"528","author":"Tan","year":"2013","journal-title":"Gene"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1046\/j.1469-1809.2002.00121.x","article-title":"Multifunctional zinc finger proteins in development and disease","volume":"66","author":"Ladomery","year":"2002","journal-title":"Ann. Hum. Genet."},{"key":"ref_23","first-page":"1217","article-title":"Modulation of the binding of progesterone receptor to DNA by polyamines","volume":"48","author":"Thomas","year":"1988","journal-title":"Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1080\/01635581.2015.990568","article-title":"Mapk genes interact with diet and lifestyle factors to alter risk of breast cancer: The breast cancer health disparities study","volume":"67","author":"Slattery","year":"2015","journal-title":"Nutr. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"248","DOI":"10.5306\/wjco.v5.i3.248","article-title":"Mechanisms and therapeutic advances in the management of endocrine-resistant breast cancer","volume":"5","author":"Zhao","year":"2014","journal-title":"World J. Clin. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.intimp.2016.10.001","article-title":"Astragaloside iv inhibits breast cancer cell invasion by suppressing vav3 mediated rac1\/mapk signaling","volume":"42","author":"Jiang","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1007\/PL00000852","article-title":"Polyamines in cell growth and cell death: Molecular mechanisms and therapeutic applications","volume":"58","author":"Thomas","year":"2001","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.toxicon.2004.02.003","article-title":"Targeting ionotropic receptors with polyamine-containing toxins","volume":"43","author":"Mellor","year":"2004","journal-title":"Toxicon"},{"key":"ref_29","first-page":"172","article-title":"Isolation, mode of action and properties of the major toxin (atraxotoxin) in the venom of the sydney funnel web spider (atrax robustus)","volume":"3","author":"Sutherland","year":"1973","journal-title":"Proc. Aust. Soc. Med. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2833","DOI":"10.1158\/0008-5472.CAN-03-2837","article-title":"Antitumor activity of 3-ingenyl angelate: Plasma membrane and mitochondrial disruption and necrotic cell death","volume":"64","author":"Ogbourne","year":"2004","journal-title":"Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"10083","DOI":"10.1158\/0008-5472.CAN-06-0348","article-title":"Induction of senescence in diterpene ester-treated melanoma cells via protein kinase c-dependent hyperactivation of the mitogen-activated protein kinase pathway","volume":"66","author":"Cozzi","year":"2006","journal-title":"Cancer Res."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/9\/11\/346\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:48:41Z","timestamp":1760208521000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/9\/11\/346"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10,27]]},"references-count":31,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2017,11]]}},"alternative-id":["toxins9110346"],"URL":"https:\/\/doi.org\/10.3390\/toxins9110346","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10,27]]}}}