{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T01:37:54Z","timestamp":1790473074851,"version":"4.1.0"},"reference-count":66,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T00:00:00Z","timestamp":1639526400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"research grant Partenariat Hubert Curien-Utique (PHC-Utique)","award":["[code 17G 0811]."],"award-info":[{"award-number":["[code 17G 0811]."]}]},{"name":"Tunisian Ministry of Higher Education and Scientific Research","award":["(LR11IPT08)"],"award-info":[{"award-number":["(LR11IPT08)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Glioblastoma is an aggressive cancer, against which medical professionals are still quite helpless, due to its resistance to current treatments. Scorpion toxins have been proposed as a promising alternative for the development of effective targeted glioblastoma therapy and diagnostic. However, the exploitation of the long peptides could present disadvantages. In this work, we identified and synthetized AaTs-1, the first tetrapeptide from Androctonus australis scorpion venom (Aa), which exhibited an antiproliferative effect specifically against human glioblastoma cells. Both the native and synthetic AaTs-1 were endowed with the same inhibiting effect on the proliferation of U87 cells with an IC50 of 0.56 mM. Interestingly, AaTs-1 was about two times more active than the anti-glioblastoma conventional chemotherapeutic drug, temozolomide (TMZ), and enhanced its efficacy on U87 cells. AaTs-1 showed a significant similarity with the synthetic peptide WKYMVm, an agonist of a G-coupled formyl-peptide receptor, FPRL-1, known to be involved in the proliferation of glioma cells. Interestingly, the tetrapeptide triggered the dephosphorylation of ERK, p38, and JNK kinases. It also enhanced the expression of p53 and FPRL-1, likely leading to the inhibition of the store operated calcium entry. Overall, our work uncovered AaTs-1 as a first natural potential FPRL-1 antagonist, which could be proposed as a promising target to develop new generation of innovative molecules used alone or in combination with TMZ to improve glioblastoma treatment response. Its chemical synthesis in non-limiting quantity represents a valuable advantage to design and develop low-cost active analogues to treat glioblastoma cancer.<\/jats:p>","DOI":"10.3390\/molecules26247610","type":"journal-article","created":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T09:02:19Z","timestamp":1639558939000},"page":"7610","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["AaTs-1: A Tetrapeptide from Androctonus australis Scorpion Venom, Inhibiting U87 Glioblastoma Cells Proliferation by p53 and FPRL-1 Up-Regulations"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8049-8950","authenticated-orcid":false,"given":"Dorra","family":"Aissaoui-Zid","sequence":"first","affiliation":[{"name":"Laboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Institut Pasteur of Tunis, University of Tunis El Manar, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed-Chiheb","family":"Saada","sequence":"additional","affiliation":[{"name":"Laboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Institut Pasteur of Tunis, University of Tunis El Manar, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wassim","family":"Moslah","sequence":"additional","affiliation":[{"name":"Laboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Institut Pasteur of Tunis, University of Tunis El Manar, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Potier-Cartereau","sequence":"additional","affiliation":[{"name":"N2C UMR 1069, INSERM, University of Tours, 37032 Tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aude","family":"Lemettre","sequence":"additional","affiliation":[{"name":"N2C UMR 1069, INSERM, University of Tours, 37032 Tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1159-6482","authenticated-orcid":false,"given":"Houcemeddine","family":"Othman","sequence":"additional","affiliation":[{"name":"Laboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Institut Pasteur of Tunis, University of Tunis El Manar, Tunis 1002, Tunisia"},{"name":"Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2041, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Gaysinski","sequence":"additional","affiliation":[{"name":"Chemistry Technological Platform NMR Department, Faculty of Sciences, University of Nice Sophia Antipolis, Parc Valrose, 06108 Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaineb","family":"Abdelkafi-Koubaa","sequence":"additional","affiliation":[{"name":"Laboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Institut Pasteur of Tunis, University of Tunis El Manar, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soumaya","family":"Souid","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Epidemiology and Experimental Pathology Applied to Infectious Diseases, LR16IPT04, Institut Pasteur of Tunis, University of Tunis El Manar, Tunis 1002, Tunisia"},{"name":"School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana, Monroe, LA 71201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naziha","family":"Marrakchi","sequence":"additional","affiliation":[{"name":"Laboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Institut Pasteur of Tunis, University of Tunis El Manar, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Vandier","sequence":"additional","affiliation":[{"name":"N2C UMR 1069, INSERM, University of Tours, 37032 Tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1371-1963","authenticated-orcid":false,"given":"Khadija","family":"Essafi-Benkhadir","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Epidemiology and Experimental Pathology Applied to Infectious Diseases, LR16IPT04, Institut Pasteur of Tunis, University of Tunis El Manar, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najet","family":"Srairi-Abid","sequence":"additional","affiliation":[{"name":"Laboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Institut Pasteur of Tunis, University of Tunis El Manar, Tunis 1002, 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