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Targeting α1 inserted domain (I) of α1β1 integrin by Lebetin 2 from M. lebetina transmediterranea venom decreased tumorigenesis and angiogenesis.

Abstract : Through the recent development of knowledge in biotechnology and bioinformatics, snake venoms are widely used to develop new drugs to treat diseases such as hypertension and cancer. We have previously reported that Lebetin 2 isolated from Macrovipera lebetina transmediterranea venom displays a potent anti-platelet activity and exerts a cardioprotective effect in ischemia-reperfusion (IR) injury model. Here, we report that Lebetin 2 possess an anti-tumor effect by targeting the integrin receptor function. It was thus able to inhibit both adhesion and migration of pheochromocytoma cells (PC12) and α1β1 integrin-expressing CHO cells (CHO-α1) to type I and IV collagens. Moreover, this peptide affects proliferation of PC12 cells by modulating AKT phosphorylation. Furthermore, Lebetin 2 exhibits a potent anti-angiogenic effect as assessed in vitro and ex vivo, using both the embryo chick chorioallantoic membrane model (CAM) and rat aortic ring assay. Interestingly, the interaction mode of Lebetin 2 with the integrin α1β1, assessed in silico, showed that the peptide represents a steric obstruction preventing the collagen from enforcing the interactions with the integrin.
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https://hal.archives-ouvertes.fr/hal-01873764
Contributor : Abdelhakim Ben Hassine <>
Submitted on : Thursday, September 13, 2018 - 3:43:33 PM
Last modification on : Wednesday, October 28, 2020 - 9:52:05 AM

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Maram Morjen, Houcemeddine Othman, Zaineb Abdelkafi-Koubaa, Erij Messadi, Jed Jebali, et al.. Targeting α1 inserted domain (I) of α1β1 integrin by Lebetin 2 from M. lebetina transmediterranea venom decreased tumorigenesis and angiogenesis.. International Journal of Biological Macromolecules, Elsevier, 2018, 117, pp.790-799. ⟨10.1016/j.ijbiomac.2018.05.230⟩. ⟨hal-01873764⟩

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