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

Maram Morjen (1) , Wassim Moslah (1) , Imen Touihri-Baraketi (2) , Najet Srairi-Abid (1) , José Luis (3) , Naziha Marrakchi (1) , Jed Jebali (1)

1 University of Tunis El Manar
2 INRAP - Institut National de Recherche et d'Analyse Physico-Chimique
3 INP - Institut de neurophysiopathologie

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.

Mots clés: Snake venom; Kunitz-type serine protease inhibitor; recombinant PIVL; tumorogenesis

Domaines: Cancer

Maram Morjen, Wassim Moslah, Imen Touihri-Baraketi, Najet Srairi-Abid, José Luis, et al.. Expression of the First Recombinant Anti-Tumoral Snake Venom Kunitz-Type Serine Protease Inhibitor. Toxins, In press, 14 (3), pp.170. ⟨10.3390/toxins14030170⟩. ⟨hal-03870820⟩