Strengthening Anti-Glioblastoma Effect by Multi-Branched Dendrimers Design of a Scorpion Venom Tetrapeptide - Archive ouverte HAL Access content directly
Journal Articles Molecules Year : 2022

Strengthening Anti-Glioblastoma Effect by Multi-Branched Dendrimers Design of a Scorpion Venom Tetrapeptide

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Wassim Moslah
  • Function : Author
  • PersonId : 1125499
Dorra Aissaoui-Zid
Soioulata Aboudou
  • Function : Author
  • PersonId : 1193770
Ines Elbini-Dhouib
Naziha Marrakchi
  • Function : Author
  • PersonId : 1124755
Didier Gigmes
  • Function : Author
  • PersonId : 956680
Christophe Vandier
  • Function : Author
  • PersonId : 917978
José Luis
Kamel Mabrouk
  • Function : Author
  • PersonId : 1140914

Abstract

Glioblastoma is the most aggressive and invasive form of central nervous system tumors due to the complexity of the intracellular mechanisms and molecular alterations involved in its progression. Unfortunately, current therapies are unable to stop its neoplastic development. In this context, we previously identified and characterized AaTs-1, a tetrapeptide (IWKS) from Androctonus autralis scorpion venom, which displayed an anti-proliferative effect against U87 cells with an IC50 value of 0.57 mM. This peptide affects the MAPK pathway, enhancing the expression of p53 and altering the cytosolic calcium concentration balance, likely via FPRL-1 receptor modulation. In this work, we designed and synthesized new dendrimers multi-branched molecules based on the sequence of AaTs-1 and showed that the di-branched (AaTs-1-2B), tetra-branched (AaTs-1-4B) and octo-branched (AaTs-1-8B) dendrimers displayed 10- to 25-fold higher effects on the proliferation of U87 cells than AaTs-1. We also found that the effects of the newly designed molecules are mediated by the enhancement of the ERK1/2 and AKT phosphorylated forms and by the increase in p53 expression. Unlike AaTs-1, AaTs-1-8B and especially AaTs-1-4B affected the migration of the U87 cells. Thus, the multi-branched peptide synthesis strategy allowed us to make molecules more active than the linear peptide against the proliferation of U87 glioblastoma cells.
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Dates and versions

hal-03870809 , version 1 (24-11-2022)

Licence

Attribution - CC BY 4.0

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Cite

Wassim Moslah, Dorra Aissaoui-Zid, Soioulata Aboudou, Zaineb Abdelkafi-Koubaa, Marie Potier-Cartereau, et al.. Strengthening Anti-Glioblastoma Effect by Multi-Branched Dendrimers Design of a Scorpion Venom Tetrapeptide. Molecules, 2022, 27 (3), pp.806. ⟨10.3390/molecules27030806⟩. ⟨hal-03870809⟩
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