{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T02:06:39Z","timestamp":1793066799016,"version":"4.5.0"},"reference-count":29,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T00:00:00Z","timestamp":1645747200000},"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>PIVL is a Kunitz-type serine protease inhibitor that was previously characterized from Tunisian snake venom, Macrovipera lebetina transmediterranea. It reduced glioblastoma cells\u2019 development and significantly blocked angiogenesis in in-vitro and ex-vivo models. PIVL exerted these effects by interfering with \u03b1v\u03b23 integrin. In order to produce a biological active recombinant, the cDNA cloning and expression of PIVL was performed in Escherichia coli (BL21)-DE3 cells using pET-22b (+) vector. The recombinant PIVL protein (rPIVL) was purified by nickel affinity chromatography and has recognized monoclonal anti-His antibody. Functionally, rPIVL exhibited potent anti-tumor cell effects as well as anti-angiogenesis properties. Interestingly, we found that both native PIVL (nPIVL) and rPIVL modulated PI3\/AKT and MAPK signaling pathways. In all, our results showed that we have successfully expressed the first active anti-oncogenic snake venom Kunitz-type protease inhibitor that can be a potential therapeutic drug against glioblastoma, in its native or recombinant form.<\/jats:p>","DOI":"10.3390\/toxins14030170","type":"journal-article","created":{"date-parts":[[2022,2,27]],"date-time":"2022-02-27T20:49:03Z","timestamp":1645994943000},"page":"170","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Expression of the First Recombinant Anti-Tumoral Snake Venom Kunitz-Type Serine Protease Inhibitor"],"prefix":"10.3390","volume":"14","author":[{"given":"Maram","family":"Morjen","sequence":"first","affiliation":[{"name":"Laboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Pasteur Institute 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, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imen","family":"Touihri-Baraketi","sequence":"additional","affiliation":[{"name":"Laboratoire des Substances Naturelles, Institut National de Recherche et d\u2019Analyse Physico-Chimique (INRAP), Sidi Thabet, Ariana 2020, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najet","family":"Srairi-Abid","sequence":"additional","affiliation":[{"name":"Laboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7419-6016","authenticated-orcid":false,"given":"Jos\u00e9","family":"Luis","sequence":"additional","affiliation":[{"name":"CNRS-UMR 7051, Institut de Neuro Physiopathologie (INP), Universit\u00e9 Aix-Marseille, 27 Bd Jean Moulin, 13385 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naziha","family":"Marrakchi","sequence":"additional","affiliation":[{"name":"Laboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis 1002, Tunisia"},{"name":"Medicine School of Tunis, University of Tunis El Manar, 15 Djebel Lakhdhar, Street La Rabta, Tunis 1007, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jed","family":"Jebali","sequence":"additional","affiliation":[{"name":"Laboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9363040","DOI":"10.1155\/2017\/9363040","article-title":"Natural Bioactive Compounds: Alternative Approach to the Treatment of Glioblastoma Multiforme","volume":"2017","author":"Desai","year":"2017","journal-title":"Biomed. 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