{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:05:39Z","timestamp":1783569939869,"version":"3.55.0"},"reference-count":54,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2018,12,1]],"date-time":"2018-12-01T00:00:00Z","timestamp":1543622400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Herm\u00ednio Ometto University Center"},{"name":"Hospital de Cancer de Barretos"},{"DOI":"10.13039\/501100004809","name":"FINEP","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicon"],"published-print":{"date-parts":[[2018,12]]},"DOI":"10.1016\/j.toxicon.2018.10.306","type":"journal-article","created":{"date-parts":[[2018,11,2]],"date-time":"2018-11-02T18:04:14Z","timestamp":1541181854000},"page":"13-22","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":44,"special_numbering":"C","title":["Crotoxin from Crotalus durissus terrificus venom: In vitro cytotoxic activity of a heterodimeric phospholipase A2 on human cancer-derived cell lines"],"prefix":"10.1016","volume":"156","author":[{"given":"Silvana Pinotti","family":"Muller","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviane Aline Oliveira","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Vit\u00f3ria Pupo","family":"Silvestrini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luana Henrique","family":"de Macedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme Ferreira","family":"Caetano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui Manuel","family":"Reis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio Ventura","family":"Mazzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.toxicon.2018.10.306_bib1","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/0167-4838(89)90189-1","article-title":"Comparative spectroscopic studies of four crotoxin homologs and their subunits","volume":"31","author":"Aird","year":"1989","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.toxicon.2018.10.306_bib2","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/S0006-2952(02)01210-8","article-title":"Structural and functional characterization of an acidic platelet aggregation inhibitor and hypotensive phospholipase A2 from Bothrops jararacacussu snake venom","volume":"64","author":"Andri\u00e3o-Escarso","year":"2002","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.toxicon.2018.10.306_bib3","first-page":"337","article-title":"Special report: studies to determine the possible antitumoral properties of cobra venom and crotoxin complex A and B","volume":"48","author":"Baldi","year":"1998","journal-title":"Medicina"},{"key":"10.1016\/j.toxicon.2018.10.306_bib4","first-page":"439","article-title":"Crotoxin, half-century of investigations on a phospholipase A2 neurotoxin","volume":"39","author":"Bon","year":"1989","journal-title":"Acta Physiol. Pharmacol. Latin. Am."},{"key":"10.1016\/j.toxicon.2018.10.306_bib5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2016\/2457532","article-title":"Walker 256 tumor growth suppression by crotoxin involves formyl peptide receptors and lipoxin A\u2084","volume":"2016","author":"Brigatte","year":"2016","journal-title":"Mediat. Inflamm."},{"key":"10.1016\/j.toxicon.2018.10.306_bib6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/203639","article-title":"Antitumoral activity of snake venom proteins: new trends in cancer therapy","volume":"2014","author":"Calderon","year":"2014","journal-title":"BioMed Res. Int."},{"key":"10.1016\/j.toxicon.2018.10.306_bib7","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0065-2571(84)90007-4","article-title":"Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors","volume":"22","author":"Chou","year":"1984","journal-title":"Adv. Enzym. Regul."},{"key":"10.1016\/j.toxicon.2018.10.306_bib8","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/BF00873905","article-title":"Cytotoxicity of crotoxin on murine erythroleukemia cells in vitro","volume":"11","author":"Corin","year":"1993","journal-title":"Invest. N. Drugs"},{"key":"10.1016\/j.toxicon.2018.10.306_bib9","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3109\/08923979809034806","article-title":"Tumor regression of advanced carcinomas following intra and or peri-tumoral inoculation with vrctc-310 in humans: preliminary report of two cases","volume":"20","author":"Costa","year":"1998","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"10.1016\/j.toxicon.2018.10.306_bib10","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1097\/00001813-199710000-00003","article-title":"Phase I study of VRCTC-310, a purified phospholipase A2 purified from snake venom, in patients with refractory cancer: safety and pharmacokinetic data","volume":"9","author":"Costa","year":"1997","journal-title":"Anti Canccer Drugs"},{"key":"10.1016\/j.toxicon.2018.10.306_bib11","doi-asserted-by":"crossref","first-page":"332","DOI":"10.21037\/tcr.2017.03.32","article-title":"Establishment and molecular characterization of short-term glioblastoma primary cultures","volume":"6","author":"Cruvinel-Carloni","year":"2017","journal-title":"Transl. Cancer Res."},{"key":"10.1016\/j.toxicon.2018.10.306_bib12","first-page":"103","article-title":"Short tandem repeat DNA typing provides an international reference standard for authentication of human cell lines","volume":"22","author":"Dirks","year":"2005","journal-title":"ALTEX"},{"key":"10.1016\/j.toxicon.2018.10.306_bib13","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1016\/0006-2952(96)00097-4","article-title":"Regulation of epidermal growth factor receptor activity by crotoxin, a snake venom phospholipase A2 toxin. A novel growth inhibitory mechanism","volume":"11","author":"Donato","year":"1996","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.toxicon.2018.10.306_bib14","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1021\/bi00402a036","article-title":"Crotoxin, a phospholipase A2 neurotoxin from the South American rattlesnake, Crotalus durissus terrificus: purification of several isoforms and comparison of their molecular structure and of their biological activities","volume":"27","author":"Faure","year":"1988","journal-title":"Biochemistry"},{"key":"10.1016\/j.toxicon.2018.10.306_bib15","doi-asserted-by":"crossref","first-page":"8074","DOI":"10.1021\/bi00246a028","article-title":"Multiplicity of acidic subunit isoforms of crotoxin, the phospholipase A2 neurotoxin from Crotalus durissus terrificus venom, results from posttranslational modifications","volume":"30","author":"Faure","year":"1991","journal-title":"Biochemistry"},{"key":"10.1016\/j.toxicon.2018.10.306_bib16","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1111\/j.1432-1033.1993.tb17946.x","article-title":"Comparison of crotoxin isoforms reveals that stability of the complex plays a major role in its pharmacological action","volume":"214","author":"Faure","year":"1993","journal-title":"Eur. J. Biochim."},{"key":"10.1016\/j.toxicon.2018.10.306_bib17","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.toxicon.2012.05.009","article-title":"Crystallographic characterization of functional sites of crotoxin and ammodytoxin, potent b-neurotoxins from Viperidae venom","volume":"60","author":"Faure","year":"2012","journal-title":"Toxicon"},{"key":"10.1016\/j.toxicon.2018.10.306_bib18","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1021\/bm8013022","article-title":"Dextrin-phospholipase A2: synthesis and evaluation as a bioresponsive anticancer conjugate","volume":"10","author":"Ferguson","year":"2009","journal-title":"Biomacromolecules"},{"key":"10.1016\/j.toxicon.2018.10.306_bib19","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/0003-9861(56)90397-6","article-title":"Fractionation and composition of crotoxin","volume":"60","author":"Fraenkel-Conrat","year":"1956","journal-title":"Arch. Biochem. Biophys."},{"key":"10.1016\/j.toxicon.2018.10.306_bib20","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1073\/pnas.68.7.1560","article-title":"Biological roles of the two components of crotoxin","volume":"68","author":"Fraenkel-Conrat","year":"1971","journal-title":"Proc. Natl. Acad. Sci. Unit. States Am."},{"key":"10.1016\/j.toxicon.2018.10.306_bib21","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1038\/aps.2014.62","article-title":"Crotoxin induces apoptosis and autophagy in human lung carcinoma cells in vitro via activation of the p38 MAPK signaling pathway","volume":"35","author":"Han","year":"2014","journal-title":"Acta Pharmacol. Sin."},{"key":"10.1016\/j.toxicon.2018.10.306_bib22","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/aps.2012.156","article-title":"Growth inhibitory effects and molecular mechanisms of crotoxin treatment in esophageal Eca-109 cells and transplanted tumors in nude mice","volume":"34","author":"He","year":"2013","journal-title":"Acta Pharmacol. Sin."},{"key":"10.1016\/j.toxicon.2018.10.306_bib23","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.toxicon.2005.07.017","article-title":"Effects of morin on snake venom phospholipase A2 (PLA2)","volume":"46","author":"Iglesias","year":"2005","journal-title":"Toxicon"},{"key":"10.1016\/j.toxicon.2018.10.306_bib24","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.canlet.2011.12.025","article-title":"Use of the \u03b3-H2AX assay to monitor DNA damage and repair in translational cancer research","volume":"327","author":"Ivashkevich","year":"2012","journal-title":"Cancer Lett."},{"key":"10.1016\/j.toxicon.2018.10.306_bib25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0171582","article-title":"Phosphorylated fraction of H2AX as a measurement for DNA damage in cancer cells and potential applications of a novel assay","volume":"12","author":"Ji","year":"2017","journal-title":"PLoS One"},{"key":"10.1016\/j.toxicon.2018.10.306_bib26","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/S0300-9084(00)01172-X","article-title":"Neuronal receptors for phospholipases A2 and b-neurotoxicity","volume":"82","author":"Krizaj","year":"2000","journal-title":"Biochimie"},{"key":"10.1016\/j.toxicon.2018.10.306_bib27","first-page":"1","article-title":"Cytotoxicity and pharmacogenomics of medicinal plants from traditional Korean medicine","volume":"2013","author":"Kuete","year":"2013","journal-title":"Evid Based Complement Alternat Med"},{"key":"10.1016\/j.toxicon.2018.10.306_bib28","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1002\/prot.21980","article-title":"Insights into the role of oligomeric state on the biological activities of crotoxin: crystal structure of a tetrameric phospholipase A2 formed by two isoforms of crotoxin B from Crotalus durissus terrificus venom","volume":"72","author":"Marchi-Salvador","year":"2008","journal-title":"Proteins"},{"key":"10.1016\/j.toxicon.2018.10.306_bib29","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1111\/j.1432-1033.1982.tb06663.x","article-title":"Relationship between the pharmacological action of crotoxin and is phospholipase activity","volume":"125","author":"Marlas","year":"1982","journal-title":"Eur. J. Biochem."},{"key":"10.1016\/j.toxicon.2018.10.306_bib30","doi-asserted-by":"crossref","first-page":"2897","DOI":"10.1007\/s00018-008-8113-3","article-title":"Cellular pathology induced by snake venom phospholipase A2 myotoxins and neurotoxins: common aspects of their mechanisms of action","volume":"65","author":"Montecucco","year":"2008","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.toxicon.2018.10.306_bib31","first-page":"170","article-title":"Crotoxin, the main toxin from venom from the Brazilian rattlesnake, Crotalus terrificus terrificus","volume":"327","author":"Neumann","year":"1955","journal-title":"Biochemist"},{"key":"10.1016\/j.toxicon.2018.10.306_bib32","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/BF00874149","article-title":"VRCTC-310, a novel compound of purified animal toxin separates antitumor efficacy from neurotoxicity","volume":"11","author":"Newman","year":"1993","journal-title":"Invest. N. Drugs"},{"key":"10.1016\/j.toxicon.2018.10.306_bib33","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.ccr.2005.03.035","article-title":"Rational design of shepherdin, a novel anticancer agent","volume":"7","author":"Plescia","year":"2005","journal-title":"Cancer Cell"},{"key":"10.1016\/j.toxicon.2018.10.306_bib34","first-page":"4142","article-title":"Vaccine site inflammation potentiates idiotype DNA vaccine-induced therapeutic T cell\u2013, and not B cell\u2013, dependent antilymphoma immunity","volume":"104","author":"Qin","year":"2016","journal-title":"Blood"},{"key":"10.1016\/j.toxicon.2018.10.306_bib35","doi-asserted-by":"crossref","first-page":"12616","DOI":"10.1016\/S0021-9258(18)33556-7","article-title":"Catalytic activity and reactivity with p-bromophenacylbromide of the phospholipase subunit of crotoxin. Influence of dimerization and association with the noncatalytic subunit","volume":"257","author":"Radvanyl","year":"1982","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.toxicon.2018.10.306_bib36","doi-asserted-by":"crossref","first-page":"894","DOI":"10.2174\/092986609788923266","article-title":"Snake venom phospholipases A2: a new class of antitumor agents","volume":"16","author":"Rodrigues","year":"2009","journal-title":"Protein Pept. Lett."},{"key":"10.1016\/j.toxicon.2018.10.306_bib37","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1007\/BF00997027","article-title":"Biochemistry and pharmacology of the crotoxin complex I. Subfractionation and recombination of the crotoxin complex","volume":"270","author":"R\u00fcbsamen","year":"1971","journal-title":"Naunyn-Schmiedebergs Arch. Pharmakol."},{"key":"10.1016\/j.toxicon.2018.10.306_bib38","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/BF00873958","article-title":"In vitro comparison of cytotoxic effects of crotoxin against three human tumors and a normal human epidermal keratinocyte cell line","volume":"12","author":"Rudd","year":"1994","journal-title":"Invest. N. Drugs"},{"key":"10.1016\/j.toxicon.2018.10.306_bib39","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.toxicon.2010.01.011","article-title":"Crotoxin: novel activities for a classic beta-neurotoxin","volume":"55","author":"Sampaio","year":"2010","journal-title":"Toxicon"},{"key":"10.1016\/j.toxicon.2018.10.306_bib40","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1021\/ac950914h","article-title":"Mass spectrometric sequencing of proteins from silver-stained polyacrylamide gels","volume":"68","author":"Shevchenko","year":"1996","journal-title":"Anal. Chem."},{"key":"10.1016\/j.toxicon.2018.10.306_bib41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mrrev.2015.07.001","article-title":"Persistent \u03b3H2AX: a promising molecular marker of DNA damage and aging","volume":"766","author":"Siddiqui","year":"2015","journal-title":"Mutat Res Rev"},{"key":"10.1016\/j.toxicon.2018.10.306_bib42","first-page":"557","article-title":"In vitro screening of cytotoxic activity of euphol from Euphorbia tirucalli on a large panel of human cancer-derived cell lines","volume":"16","author":"Silva","year":"2018","journal-title":"Exper. and Ther. Med."},{"key":"10.1016\/j.toxicon.2018.10.306_bib43","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s13402-016-0270-z","article-title":"Cytotoxicity of allitinib, an irreversible anti-EGFR agent, in a large panel of human cancer-derived cell lines: KRAS mutation status as a predictive biomarker","volume":"39","author":"Silva-Oliveira","year":"2016","journal-title":"Cell. Oncol."},{"key":"10.1016\/j.toxicon.2018.10.306_bib44","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.toxicon.2003.11.004","article-title":"Chemical modifications of phospholipases A2 from snake venoms: effects on catalytic and pharmacological properties","volume":"42","author":"Soares","year":"2003","journal-title":"Toxicon"},{"key":"10.1016\/j.toxicon.2018.10.306_bib45","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.2174\/1389201017666160808154250","article-title":"Antitumoral potential of snake venom phospholipases A2 and synthetic peptides","volume":"17","author":"Sobrinho","year":"2016","journal-title":"Curr. Pharmaceut. Biotechnol."},{"key":"10.1016\/j.toxicon.2018.10.306_bib46","series-title":"Methods in Plant Biochemistry: Assays for Bioactivity","first-page":"71","article-title":"Assays related to cancer drug discovery","author":"Suffness","year":"1990"},{"key":"10.1016\/j.toxicon.2018.10.306_bib47","doi-asserted-by":"crossref","first-page":"33","DOI":"10.3797\/scipharm.0912-11","article-title":"Antiproliferative activity of plant extracts used against cancer in traditional medicine","volume":"78","author":"Talib","year":"2010","journal-title":"Sci. Pharm."},{"key":"10.1016\/j.toxicon.2018.10.306_bib48","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.toxicon.2016.06.009","article-title":"Isolation, characterization and screening of the in vitro cytotoxic activity of a novel L-amino acid oxidase (LAAOcdt) from Crotalus durissus terrificus venom on human cancer cell lines","volume":"119","author":"Teixeira","year":"2016","journal-title":"Toxicon"},{"key":"10.1016\/j.toxicon.2018.10.306_bib49","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1007\/s40265-015-0489-4","article-title":"Recent advances in the development of antineoplastic agents derived from natural products","volume":"75","author":"Trendowski","year":"2015","journal-title":"Drugs"},{"key":"10.1016\/j.toxicon.2018.10.306_bib50","doi-asserted-by":"crossref","first-page":"153","DOI":"10.4251\/wjgo.v3.i11.153","article-title":"Molecular predictors of gemcitabine response in pancreatic cancer","volume":"3","author":"Voutsadakis","year":"2011","journal-title":"World J. Gastrointest. Oncol."},{"key":"10.1016\/j.toxicon.2018.10.306_bib51","first-page":"1341","article-title":"Crotoxin enhances the antitumor activity of gefinitib (Iressa) in SK-MES-1 human lung squamous carcinoma cells","volume":"27","author":"Wang","year":"2012","journal-title":"Oncol. Rep."},{"key":"10.1016\/j.toxicon.2018.10.306_bib52","doi-asserted-by":"crossref","first-page":"133","DOI":"10.2147\/CMAR.S32199","article-title":"New and emerging combination therapies for esophageal cancer","volume":"5","author":"Wiedmann","year":"2013","journal-title":"Cancer Manag. Res."},{"key":"10.1016\/j.toxicon.2018.10.306_bib53","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1111\/j.1745-7254.2007.00530.x","article-title":"Autophagy is involved in cytotoxic effects of crotoxin in human breast cancer cell line MCF-7 cells","volume":"28","author":"Yan","year":"2007","journal-title":"Acta Pharm."},{"key":"10.1016\/j.toxicon.2018.10.306_bib54","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1038\/aps.2011.116","article-title":"Anti-tumor activity of CTX in human lung adenocarcinoma cell line A549","volume":"32","author":"Ye","year":"2011","journal-title":"Acta Pharmacol. Sin."}],"container-title":["Toxicon"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041010118307141?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041010118307141?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T04:10:31Z","timestamp":1662351031000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0041010118307141"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12]]},"references-count":54,"alternative-id":["S0041010118307141"],"URL":"https:\/\/doi.org\/10.1016\/j.toxicon.2018.10.306","relation":{},"ISSN":["0041-0101"],"issn-type":[{"value":"0041-0101","type":"print"}],"subject":[],"published":{"date-parts":[[2018,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Crotoxin from Crotalus durissus terrificus venom: In vitro cytotoxic activity of a heterodimeric phospholipase A2 on human cancer-derived cell lines","name":"articletitle","label":"Article Title"},{"value":"Toxicon","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.toxicon.2018.10.306","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}