{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:08:54Z","timestamp":1788314934452,"version":"build-2803163510"},"reference-count":30,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T00:00:00Z","timestamp":1742947200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Consejo Nacional de Ciencia y Tecnolog\u00eda (CONACyT)","award":["318968"],"award-info":[{"award-number":["318968"]}]},{"name":"Consejo Nacional de Ciencia y Tecnolog\u00eda (CONACyT)","award":["819358"],"award-info":[{"award-number":["819358"]}]},{"name":"Consejo Nacional de Ciencia y Tecnolog\u00eda (CONACyT)","award":["UACH-24-10"],"award-info":[{"award-number":["UACH-24-10"]}]},{"name":"Universidad Aut\u00f3noma de Chihuahua (UACh) research program +UACH, +Ciencia","award":["318968"],"award-info":[{"award-number":["318968"]}]},{"name":"Universidad Aut\u00f3noma de Chihuahua (UACh) research program +UACH, +Ciencia","award":["819358"],"award-info":[{"award-number":["819358"]}]},{"name":"Universidad Aut\u00f3noma de Chihuahua (UACh) research program +UACH, +Ciencia","award":["UACH-24-10"],"award-info":[{"award-number":["UACH-24-10"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Breast cancer remains the leading cause of cancer-related mortality among women worldwide, with limited therapeutic efficacy due to treatment resistance and adverse effects. Emerging evidence suggests that ion channels play crucial roles in tumor progression, regulating proliferation, apoptosis, migration, and metastasis. Voltage-gated potassium (Kv) and sodium (Nav) channels have been implicated in oncogenic signaling pathways. Scorpion venom peptides, known for their selective ion-channel-blocking properties, have demonstrated promising antineoplastic activity. This study explores the potential therapeutic applications of bioactive fractions derived from Chihuahuanus coahuilae, in breast cancer cell lines. Through chromatographic separation, mass spectrometry, and functional assays, we assess their effects on cell viability, proliferation, and ion channel modulation. Our preliminary data suggest that these venom-derived peptides interfere with cancer cell homeostasis by altering ion fluxes, promoting apoptosis, and inhibiting metastatic traits. These findings support the therapeutic potential of ion-channel-targeting peptides as selective anticancer agents. Further investigations into their molecular mechanisms may pave the way for novel, targeted therapies with improved efficacy and specificity for breast cancer treatment.<\/jats:p>","DOI":"10.3390\/toxins17040166","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T06:58:43Z","timestamp":1742972323000},"page":"166","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Ion-Channel-Targeting Scorpion Recombinant Toxin as Novel Therapeutic Agent for Breast Cancer"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8518-5306","authenticated-orcid":false,"given":"Natalia","family":"Mata de los Rios","sequence":"first","affiliation":[{"name":"Traslational Research Laboratory, Facultad de Medicina y Ciencias Biom\u00e9dicas, Autonomous University of Chihuahua, Circuito Universitario s\/n, Campus II, Chihuahua 31125, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2745-6783","authenticated-orcid":false,"given":"Argel","family":"Gastelum-Arellanez","sequence":"additional","affiliation":[{"name":"Facultad de Medicina y Ciencias Biom\u00e9dicas, Autonomous University of Chihuahua, Circuito Universitario s\/n, Campus II, Chihuahua 31125, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7671-813X","authenticated-orcid":false,"given":"Herlinda","family":"Clement","sequence":"additional","affiliation":[{"name":"Instituto de Biotecnolog\u00eda\u2014UNAM, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Av. Universidad 2001, Col. Chamilpa, Cuernavaca 62210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karely","family":"\u00c1lvarez-Cruz","sequence":"additional","affiliation":[{"name":"Traslational Research Laboratory, Facultad de Medicina y Ciencias Biom\u00e9dicas, Autonomous University of Chihuahua, Circuito Universitario s\/n, Campus II, Chihuahua 31125, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Romero-Terrazas","sequence":"additional","affiliation":[{"name":"Traslational Research Laboratory, Facultad de Medicina y Ciencias Biom\u00e9dicas, Autonomous University of Chihuahua, Circuito Universitario s\/n, Campus II, Chihuahua 31125, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0308-046X","authenticated-orcid":false,"given":"Carolina","family":"Alvarado-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Traslational Research Laboratory, Facultad de Medicina y Ciencias Biom\u00e9dicas, Autonomous University of Chihuahua, Circuito Universitario s\/n, Campus II, Chihuahua 31125, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4229-5140","authenticated-orcid":false,"given":"Luis Carlos","family":"Hinojos-Gallardo","sequence":"additional","affiliation":[{"name":"Facultad de Medicina y Ciencias Biom\u00e9dicas, Autonomous University of Chihuahua, Circuito Universitario s\/n, Campus II, Chihuahua 31125, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9513-1622","authenticated-orcid":false,"given":"Gerardo","family":"Corzo","sequence":"additional","affiliation":[{"name":"Instituto de Biotecnolog\u00eda\u2014UNAM, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Av. Universidad 2001, Col. Chamilpa, Cuernavaca 62210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9549-0676","authenticated-orcid":false,"given":"Gerardo P\u00e1vel","family":"Espino-Solis","sequence":"additional","affiliation":[{"name":"Traslational Research Laboratory, Facultad de Medicina y Ciencias Biom\u00e9dicas, Autonomous University of Chihuahua, Circuito Universitario s\/n, Campus II, Chihuahua 31125, Mexico"},{"name":"Laboratorio Nacional de Citometr\u00eda de Flujo, Facultad de Medicina y Ciencias Biom\u00e9dicas, Autonomous University of Chihuahua, Circuito Universitario s\/n, Campus II, Chihuahua 31125, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,26]]},"reference":[{"key":"ref_1","unstructured":"(2023, September 14). OMS C\u00e1ncer. Available online: https:\/\/www.who.int\/es\/news-room\/fact-sheets\/detail\/cancer."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"106535","DOI":"10.1016\/j.intimp.2020.106535","article-title":"Breast Cancer: Biology, Biomarkers, and Treatments","volume":"84","author":"Barzaman","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1097\/01.JAA.0000580524.95733.3d","article-title":"Overview of Breast Cancer","volume":"32","author":"Watkins","year":"2019","journal-title":"JAAPA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"20211033","DOI":"10.1259\/bjr.20211033","article-title":"Understanding Breast Cancer as a Global Health Concern","volume":"95","author":"Wilkinson","year":"2022","journal-title":"Br. J. Radiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of Cancer: The Next Generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"D\u00edaz-Garc\u00eda, A., and Varela, D. (2020). Voltage-Gated K+\/Na+ Channels and Scorpion Venom Toxins in Cancer. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00913"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.toxicon.2014.11.233","article-title":"Scorpion Venom Components as Potential Candidates for Drug Development","volume":"93","author":"Ortiz","year":"2015","journal-title":"Toxicon"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"84","DOI":"10.52547\/ibj.3863","article-title":"Peptides with Diverse Functions from Scorpion Venom: A Great Opportunity for the Treatment of a Wide Variety of Diseases","volume":"27","author":"Baradaran","year":"2023","journal-title":"Iran. Biomed. J."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ageitos, L., Torres, M.D.T., and de la Fuente-Nunez, C. (2022). Biologically Active Peptides from Venoms: Applications in Antibiotic Resistance, Cancer, and Beyond. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232315437"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Alvarado-Gonzalez, C., Clement, H., Ballinas-Casarrubias, L., Escarcega-Avila, A., Arenas-Sosa, I., Lopez-Contreras, K.S., Zamudio, F., Corzo, G., and Espino-Solis, G.P. (2023). Identification and Venom Characterization of Two Scorpions from the State of Chihuahua Mexico: Chihuahuanus Coahuliae and Chihuahuanus Crassimannus. Toxins, 15.","DOI":"10.3390\/toxins15070416"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Ahmadi, S., Knerr, J.M., Argemi, L., Bordon, K.C.F., Pucca, M.B., Cerni, F.A., Arantes, E.C., \u00c7al\u0131\u015fkan, F., and Laustsen, A.H. (2020). Scorpion Venom: Detriments and Benefits. Biomedicines, 8.","DOI":"10.3390\/biomedicines8050118"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Rezaei, A., Asgari, S., Komijani, S., Sadat, S.N., Sabatier, J.-M., Nasrabadi, D., Pooshang Bagheri, K., Shahbazzadeh, D., Akbari Eidgahi, M.R., and De Waard, M. (2022). Discovery of Leptulipin, a New Anticancer Protein from TheIranian Scorpion, Hemiscorpius Lepturus. Molecules, 27.","DOI":"10.3390\/molecules27072056"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.1016\/j.bbamem.2018.08.012","article-title":"Biophysical Characterization and Antitumor Activity of Synthetic Pantinin Peptides from Scorpion\u2019s Venom","volume":"1860","author":"Crusca","year":"2018","journal-title":"Biochim. Biophys. Acta (BBA)-Biomembranes"},{"key":"ref_14","first-page":"192","article-title":"In-Vitro Study of Hottentotta Schach Crude Venom Anticancer Effects on MCF-7 and Vero Cell Lines","volume":"19","author":"Dezianian","year":"2020","journal-title":"Iran. J. Pharm. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1016\/j.tiv.2011.09.002","article-title":"Scorpion Venom (Odontobuthus Doriae) Induces Apoptosis by Depolarization of Mitochondria and Reduces S-Phase Population in Human Breast Cancer Cells (MCF-7)","volume":"25","author":"Zargan","year":"2011","journal-title":"Toxicol. In Vitro"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"105","DOI":"10.4314\/ajtcam.v11i5.17","article-title":"Inhibition Effects of Scorpion Venom Extracts (&lt;I&gt;Buthus Matensii&lt;\/I&gt; Karsch) on the Growth of Human Breast Cancer MCF-7 Cells","volume":"11","author":"Li","year":"2014","journal-title":"Afr. J. Tradit. Complement. Altern. Med."},{"key":"ref_17","first-page":"9","article-title":"Rhopalurus Junceus Scorpion Venom Induces Apoptosis in the Triple Negative Human Breast Cancer Cell Line MDA-MB-231","volume":"8","year":"2017","journal-title":"J. Venom. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1046\/j.1432-1327.1999.00625.x","article-title":"Scorpion Toxins Specific for Na + -channels","volume":"264","author":"Possani","year":"1999","journal-title":"Eur. J. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1073\/pnas.88.6.2046","article-title":"Design, Synthesis, and Functional Expression of a Gene for Charybdotoxin, a Peptide Blocker of K+ Channels","volume":"88","author":"Park","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.toxicon.2005.09.006","article-title":"Overview of Scorpion Toxins Specific for Na+ Channels and Related Peptides: Biodiversity, Structure\u2013Function Relationships and Evolution","volume":"46","author":"Possani","year":"2005","journal-title":"Toxicon"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.toxicon.2006.11.016","article-title":"The Differential Preference of Scorpion \u03b1-Toxins for Insect or Mammalian Sodium Channels: Implications for Improved Insect Control","volume":"49","author":"Gordon","year":"2007","journal-title":"Toxicon"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.toxicon.2013.07.012","article-title":"Scorpion Venom Components That Affect Ion-Channels Function","volume":"76","author":"Gurrola","year":"2013","journal-title":"Toxicon"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1186\/1476-4598-13-264","article-title":"Ranolazine Inhibits NaV1.5-Mediated Breast Cancer Cell Invasiveness and Lung Colonization","volume":"13","author":"Driffort","year":"2014","journal-title":"Mol. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1007\/s11095-008-9782-1","article-title":"Maurocalcine as a Non Toxic Drug Carrier Overcomes Doxorubicin Resistance in the Cancer Cell Line MDA-MB 231","volume":"26","author":"Aroui","year":"2009","journal-title":"Pharm. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/s10549-012-2102-9","article-title":"Therapeutic Potential for Phenytoin: Targeting Nav1.5 Sodium Channels to Reduce Migration and Invasion in Metastatic Breast Cancer","volume":"134","author":"Yang","year":"2012","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5381","DOI":"10.1158\/1078-0432.CCR-05-0327","article-title":"Voltage-Gated Sodium Channel Expression and Potentiation of Human Breast Cancer Metastasis","volume":"11","author":"Fraser","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1046\/j.1365-3083.2000.00653.x","article-title":"Toremifene Increases the Expression of Intercellular Adhesion Molecule-1 (ICAM-1) on MCF-7 Breast Cancer Cells and Jurkat Cells","volume":"51","author":"Komi","year":"2000","journal-title":"Scand. J. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Roger, S., Gillet, L., Le Guennec, J.-Y., and Besson, P. (2015). Voltage-Gated Sodium Channels and Cancer: Is Excitability Their Primary Role?. Front. Pharmacol., 6.","DOI":"10.3389\/fphar.2015.00152"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.pep.2018.09.004","article-title":"CDNA Cloning, Heterologous Expression, Protein Folding and Immunogenic Properties of a Phospholipase A2 from Bothrops Ammodytoides Venom","volume":"154","author":"Clement","year":"2019","journal-title":"Protein Expr. Purif."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Herberich, E., Sikorski, J., and Hothorn, T. (2010). A Robust Procedure for Comparing Multiple Means under Heteroscedasticity in Unbalanced Designs. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009788"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/17\/4\/166\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:00:26Z","timestamp":1760029226000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/17\/4\/166"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,26]]},"references-count":30,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["toxins17040166"],"URL":"https:\/\/doi.org\/10.3390\/toxins17040166","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,26]]}}}