AaTs-1: A Tetrapeptide from Androctonus australis Scorpion Venom, Inhibiting U87 Glioblastoma Cells Proliferation by p53 and FPRL-1 Up-Regulations - Archive ouverte HAL Access content directly
Journal Articles Molecules Year : 2021

AaTs-1: A Tetrapeptide from Androctonus australis Scorpion Venom, Inhibiting U87 Glioblastoma Cells Proliferation by p53 and FPRL-1 Up-Regulations

(1, 2) , (1, 2) , (1, 2) , (3) , (3) , (1, 2, 4) , (5) , (1, 2) , (6, 7) , (1, 2) , (3) , (6) , (1, 2)
1
2
3
4
5
6
7
Aude Lemettre
  • Function : Author
  • PersonId : 1124902
Christophe Vandier
  • Function : Author
  • PersonId : 917978

Abstract

Glioblastoma is an aggressive cancer, against which medical professionals are still quite helpless, due to its resistance to current treatments. Scorpion toxins have been proposed as a promising alternative for the development of effective targeted glioblastoma therapy and diagnostic. However, the exploitation of the long peptides could present disadvantages. In this work, we identified and synthetized AaTs-1, the first tetrapeptide from Androctonus australis scorpion venom (Aa), which exhibited an antiproliferative effect specifically against human glioblastoma cells. Both the native and synthetic AaTs-1 were endowed with the same inhibiting effect on the proliferation of U87 cells with an IC50 of 0.56 mM. Interestingly, AaTs-1 was about two times more active than the anti-glioblastoma conventional chemotherapeutic drug, temozolomide (TMZ), and enhanced its efficacy on U87 cells. AaTs-1 showed a significant similarity with the synthetic peptide WKYMVm, an agonist of a G-coupled formyl-peptide receptor, FPRL-1, known to be involved in the proliferation of glioma cells. Interestingly, the tetrapeptide triggered the dephosphorylation of ERK, p38, and JNK kinases. It also enhanced the expression of p53 and FPRL-1, likely leading to the inhibition of the store operated calcium entry. Overall, our work uncovered AaTs-1 as a first natural potential FPRL-1 antagonist, which could be proposed as a promising target to develop new generation of innovative molecules used alone or in combination with TMZ to improve glioblastoma treatment response. Its chemical synthesis in non-limiting quantity represents a valuable advantage to design and develop low-cost active analogues to treat glioblastoma cancer.
Fichier principal
Vignette du fichier
009.pdf (29.86 Mo) Télécharger le fichier
Origin : Publication funded by an institution

Dates and versions

pasteur-03550568 , version 1 (01-02-2022)

Licence

Attribution - CC BY 4.0

Identifiers

Cite

Dorra Aissaoui-Zid, Mohamed-Chiheb Saada, Wassim Moslah, Marie Potier-Cartereau, Aude Lemettre, et al.. AaTs-1: A Tetrapeptide from Androctonus australis Scorpion Venom, Inhibiting U87 Glioblastoma Cells Proliferation by p53 and FPRL-1 Up-Regulations. Molecules, 2021, 26 (24), pp.7610. ⟨10.3390/molecules26247610⟩. ⟨pasteur-03550568⟩
6 View
15 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More