Expression of the First Recombinant Anti-Tumoral Snake Venom Kunitz-Type Serine Protease Inhibitor.

Abstract

PIVL is a Kunitz-type serine protease inhibitor that was previously characterized from Tunisian snake venom, Macrovipera lebetina transmediterranea. It reduced glioblastoma cells' development and significantly blocked angiogenesis in in-vitro and ex-vivo models. PIVL exerted these effects by interfering with αvβ3 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.

• Authors: Maram Morjen, Wassim Moslah, Imen Touihri-Baraketi, Najet Srairi-Abid, José Luis, Naziha Marrakchi, Jed Jebali
• Journal: Toxins (Toxins (Basel)) Vol. 14 Issue 3 (02 25 2022) ISSN: 2072-6651 [Electronic] Switzerland
• PMID: 35324668 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antivenins
• Serine Proteinase Inhibitors
• Snake Venoms
• Serine

Topics

• Antivenins
• Glioblastoma (drug therapy)
• Humans
• Serine
• Serine Proteinase Inhibitors (chemistry, genetics, pharmacology)
• Snake Venoms