{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T04:19:13Z","timestamp":1787804353538,"version":"build-2784847793"},"reference-count":41,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100006181","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado da Bahia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006181","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Malignant glioma is the most common primary brain tumor, and glioblastoma multiforme (GBM) remains its most aggressive and incurable form. Snake venoms contain bioactive compounds with promising antitumoral properties against several cancer types. This study investigated the in\u00a0vitro antitumor activity of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Bothrops leucurus<\/jats:italic>\n                    <\/jats:styled-content>\n                    crude venom against rat and human glioma cells and identified two active venom enzymes. The crude venom showed concentration\u2010dependent cytotoxicity, with EC\n                    <jats:sub>50<\/jats:sub>\n                    values of 2.66\u2009\u03bcg\/mL for rat glioma cells and 3.60\u2009\u03bcg\/mL for human U251 glioma cells after 72\u2009h. At 3.0\u2009\u03bcg\/mL, the venom induced necrotic death in glioma cells, whereas astrocytes remained viable. Two enzymes with anti\u2010glioma activity were identified: the metalloprotease P\u2010III leucurolysin\u2010B and a basic phospholipase A\n                    <jats:sub>2<\/jats:sub>\n                    (bPLA\n                    <jats:sub>2<\/jats:sub>\n                    ). Both enzymes exhibited concentration\u2010dependent cytotoxicity toward C6 and U251 glioma cells. Leucurolysin\u2010B was more potent than bPLA\n                    <jats:sub>2<\/jats:sub>\n                    , presenting EC\n                    <jats:sub>50<\/jats:sub>\n                    values of 1.44 and 2.25\u2009\u03bcg\/mL for C6 and U251 cells, respectively, while bPLA\n                    <jats:sub>2<\/jats:sub>\n                    showed EC\n                    <jats:sub>50<\/jats:sub>\n                    values of 30.00 and 39.81\u2009\u03bcg\/mL. Treatment with both enzymes reduced cellularity and induced morphological alterations in glioma cells without affecting healthy human astrocytes, indicating selective activity. Leucurolysin\u2010B primarily induced apoptosis, whereas bPLA\n                    <jats:sub>2<\/jats:sub>\n                    mainly caused necrosis. These findings demonstrate the antitumor potential of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>B. leucurus<\/jats:italic>\n                    <\/jats:styled-content>\n                    venom, particularly leucurolysin\u2010B, as a promising candidate for glioma therapy development. Overall, the results suggest that venom\u2010derived molecules may represent prototypes for developing therapies against malignant gliomas, combining efficacy with reduced toxicity toward normal glial cells. Further studies are required to clarify their mechanisms of action and evaluate their potential experimentally.\n                  <\/jats:p>","DOI":"10.1002\/jat.70409","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T03:53:32Z","timestamp":1787802812000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Crude Venom of the Whitetail Lancehead,\n                    <scp>\n                      <i>Bothrops leucurus<\/i>\n                    <\/scp>\n                    , and Two of Its Enzymatic Components Are Selectively Cytotoxic for Glioma Cells In\u00a0Vitro"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0043-5210","authenticated-orcid":false,"given":"M. O. H. V.","family":"Ros\u00e1rio","sequence":"first","affiliation":[{"name":"Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics Institute of Health Sciences, Federal University of Bahia  Salvador Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. M.","family":"Fucase","sequence":"additional","affiliation":[{"name":"Biotechnology Center Institute for Energy and Nuclear Research (IPEN)  S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8949-7735","authenticated-orcid":false,"given":"P. J.","family":"Spencer","sequence":"additional","affiliation":[{"name":"Biotechnology Center Institute for Energy and Nuclear Research (IPEN)  S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7213-206X","authenticated-orcid":false,"given":"J. M.","family":"Sciani","sequence":"additional","affiliation":[{"name":"San Francisco University  Bragan\u00e7a Paulista Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Clar\u00eancio","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology and Immunoregulation Gon\u00e7alo Moniz Research Center  Salvador Bahia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9210-092X","authenticated-orcid":false,"given":"G.","family":"R\u00e1dis\u2010Baptista","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics Institute of Health Sciences, Federal University of Bahia  Salvador Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3746-1348","authenticated-orcid":false,"given":"L. L.","family":"Casais\u2010e\u2010Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroimmunoendocrinology and Toxinology, Department of Bioregulation Institute of Health Sciences, Federal University of Bahia  Salvador Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3321-0392","authenticated-orcid":false,"given":"R. S.","family":"El\u2010Bach\u00e1","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics Institute of Health Sciences, Federal University of Bahia  Salvador Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2018.12.005"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2014.02.018"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2009.03.007"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201011\u20100153"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201062620\u20109"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/203639"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024\u20103205(87)90126\u20103"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.15309"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.2741\/S261"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0887\u20102333(94)90156\u20102"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2008.05.021"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/0962935029000041"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2019.05.164"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12094\u2010016\u20101497\u2010x"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1590\/1678\u20109199\u2010JVATITD\u20102021\u20100094"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1590\/S1678-91992012000100004"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10030484"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2011.05.013"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590\u2010019\u20100433\u2010y"},{"issue":"3","key":"e_1_2_10_21_1","first-page":"249","article-title":"In Vitro Studies on Bothrops Venoms Cytotoxic Effect on Tumor Cells","volume":"9","author":"Jorge R. J.","year":"2011","journal-title":"Journal of Experimental Therapeutics & Oncology"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2011.09.005"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2003.11.002"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/pl00006450"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2021.109622"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins10090346"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010007\u20100243\u20104"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389201021666200717092207"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2023.107547"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022\u20101759(83)90303\u20104"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2011.04.003"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2012.03.002"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11910\u2010021\u201001152\u20109"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40409\u2010015\u20100044\u20105"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.3171\/jns.2005.103.3.0526"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2016.204"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpneuro0289"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(09)70025\u20107"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043330"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2009.09.004"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13402\u2010026\u201001252\u2010z"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2009.01.003"}],"container-title":["Journal of Applied Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.70409","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jat.70409","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.70409","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T03:53:39Z","timestamp":1787802819000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jat.70409"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,26]]},"references-count":41,"alternative-id":["10.1002\/jat.70409"],"URL":"https:\/\/doi.org\/10.1002\/jat.70409","archive":["Portico"],"relation":{},"ISSN":["0260-437X","1099-1263"],"issn-type":[{"value":"0260-437X","type":"print"},{"value":"1099-1263","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,26]]},"assertion":[{"value":"2026-06-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"jat.70409"}}