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.

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.

The emerging concept of small conductance Ca²⁺-activated potassium channels (SK_Ca) as pharmacological target for cancer treatment has significantly increased in recent years. In this study, we isolated the P01 toxin from Androctonus australis (Aa) scorpion venom and investigated its effect on biological properties of glioblastoma U87, breast MDA-MB231 and colon adenocarcinoma LS174 cancer cell lines. Our results showed that P01 was active only on U87 glioblastoma cells. It inhibited their proliferation, adhesion and migration with IC₅₀ values in the micromolar range. We have also shown that P01 reduced the amplitude of the currents recorded in HEK293 cells expressing SK2 channels with an IC₅₀ value of 3 pM, while it had no effect on those expressing SK3 channels. The investigation of the SK_Ca channels expression pattern showed that SK2 transcripts were expressed differently in the three cancer cell lines. Particularly, we highlighted the presence of SK2 isoforms in U87 cells, which could explain and rely on the specific activity of P01 on this cell line. These experimental data highlighted the usefulness of scorpion peptides to decipher the role of SK_Ca channels in the tumorigenesis process, and develop potential therapeutic molecules targeting glioblastoma with high selectivity.

Providing pathogen-free ready-to-eat (RTE) salads is critical for all consumers, especially individuals with weakened immunity. In this study, the efficacy of γ-irradiation on Staphylococcus aureus (S. aureus) in freshly packaged salads (4.24 log CFU/g) treated with essential oil (EO) and myrtle juice during 10 days of storage and their impact on organoleptic properties were investigated. EO was extracted by hydrodistillation and the chemical composition was analyzed by gas chromatography with Flame Ionization Detector (GC/FID) and gas chromatography/mass spectrometry (GC/MS). Myrtle juice was prepared from fresh fruits. The cytotoxic effects of Thymus capitatus (T. capitatus) EO against a normal human umbilical vein endothelial cell (HUVEC) were assessed. GC/FID and GC-MS analysis of the thyme EO revealed the presence of 13 compounds, including carvacrol (79.55%) and p-cymene (7.93%) as major components. The EO was found to be non-cytotoxic, with concentrations lower than 0.16 µL/mL. A reduction of more than 3 log CFU/g and a total inactivation of S. aureus were achieved with the combination of gamma irradiation at 0.5 kGy with myrtle juice at 6 µL/mL and EO at 0.08 µL/mL respectively. The treatment of fresh RTE salads with thyme and myrtle juice was evaluated as acceptable by the sensory panel. The combined effect showed a synergistic potential on the inactivation of S. aureus.