EXTH-51. Snake venom bioprospecting as an approach to finding potential anti-glioblastoma molecules: evaluation of the antitumoral effect of the disintegrin lansbermin-I from the venom of the snake Porthidium lansbergii in tumor cell lines of Glioblastoma and non-tumorigenic astrocytic lines

We isolated for the first time Lansbermin-I, an RGD-type disintegrin, from the venom of the snake Porthidium lansbergii, obtained by HPLC and sequenced by mass spectrometry. We used T98G Glioblastoma(GB) cell line from ECACC. We demonstrated that the cytotoxicity of Lansbermin-I was higher than that of Temozolamide (TMZ) at concentrations ranging from 12.5 μg/ml to 100 μg/ml; at the highest concentration of both molecules, Lansbermin-I cytotoxicity was 38.1%, vs. 34.9% induced by TMZ. This concentration in molarity is 30 times lower compared to the same concentration of TMZ (13.18 μM vs 515.06 μM). This could be an indication that fewer Lansbermin-I molecules are required to interact with critical membrane receptors in GB cell viability. Lansbermin-I generated a less toxic effect than TMZ on astrocyte cell line at the highest concentrations, 28% vs 37%. Lansbermin-I induced cell cycle arrest in T98G cells, increasing cells in G1 phase from 91.4% to 95.16%, reducing proportion of cells in S phase from 3.1% to 1.15% and G2/M phase from 4.3% to 2.26%. The apoptotic effect of Lansbermin-I on T98G cells was confirmed by flow cytometry using Annexin V–FITC and 7-AAD. The proportion of T98G cells with apoptosis was increased following Lansbermin-I treatment compared to the control after 24 hours of incubation (7.5% vs 42%). The 3D model of Lansbermin-I was generated by sequence homology using SWISSMODEL, by Expasy server. Molecular docking between Lansbermin-I and the integrin αvβ3, as well as Fibronoectin and the integrin itself, was simulated using the ClusPro server version 2.0. Lansbermin-I shows a high interaction with the integrin αvβ3 and in competing with fibronectin for the binding site. CONCLUSION Lansbermin-I has potential as a therapeutic agent against GB, based on its concentration-dependent cytotoxicity and limited impact on astrocyte cell lines, indicating possible selectivity toward tumor cells.