Scorpion Venom Antimicrobial Peptides Induce Caspase-1 Dependant Pyroptotic Cell Death

Abstract

Within the last decade, several peptides have been identified according to their ability to inhibit the growth of microbial pathogens. These antimicrobial peptides (AMPs) are a part of the innate immune system of all living organisms. Many studies on their effects on prokaryotic microorganisms have been reported; some of these peptides have cytotoxic properties although the molecular mechanisms underlying their activity on eukaryotic cells remain poorly understood. Smp24 and Smp43 are novel cationic AMPs which were identified from the venom of the Egyptian scorpion Scorpio maurus palmatus. Smp24 and Smp43 showed potent activity against both Gram-positive and Gram-negative bacteria as well as fungi. Here we describe cytotoxicity of these peptides towards two acute leukaemia cell lines (myeloid (KG1-a) and lymphoid (CCRF-CEM) leukaemia cell lines) and three non-tumour cell lines CD34+ (hematopoietic stem progenitor from cord blood), HRECs (human renal epithelial cells) and HaCaT (human skin keratinocytes). Smp24 and Smp43 (4–256 µg/ml) decreased the viability of all cell lines, although HaCaT cells were markedly less sensitive. With the exception HaCaT cells, the caspase-1 gene was uniquely up-regulated in all cell lines studied. However, all cell lines showed an increase in downstream interleukin-1β (IL-1β) expression. Transmission electron microscope studies revealed the formation of cell membrane blebs and the appearance of autolysosomes and lipid droplets in all cell lines; KG1-a leukemia cells also showed the unique appearance of glycogen deposits. Our results reveal a novel mechanism of action for scorpion venom AMPs, activating a cascade of events leading to cell death through a programmed pyroptotic mechanism.

Smp24, a Scorpion-Venom Peptide, Exhibits Potent Antitumor Effects against Hepatoma HepG2 Cells via Multi-Mechanisms In Vivo and In Vitro

“…DAPI, cyclosporin A (CsA, an inhibitor of permeability transition), N-acetyl-L-cysteine (NAC), ROS assay kit, LDH-release assay kit, cell cycle and apoptosis analysis kit, and mitochondrial membrane potential assay kit for JC-1 were bought from Beyotime Institute of Biotechnology (Shanghai, China). Smp24 and FITC-labeled Smp24 were obtained as previously described by us [ 9 ].…”

“…We previously reported Smp24 (IWSFLIKAATKLLPSLFGGGKKDS), a cationic AMP identified from the venom of Scorpio Maurus palmatus with a wide antimicrobial spectrum against various bacteria and fungi [ 8 ]. The cytotoxicity of Smp24 against two acute leukemia cell lines (KG1-a and CCRF-CEM), as well as four lung cancer cell lines (A549, H3122, PC-9, and H460) and nontumor cell lines (HRECs, CD34 + , MCR-5, and HaCaT) has been described in further studies [ 9 , 10 , 11 ]. Smp24 also has cytotoxic effects against HepG2 hepatoma cells, as presented in ATP release assays; nevertheless, its mode of action against HepG2 hepatoma cells remains unclear.…”

Recalculating the Route: Repositioning Antimicrobial Peptides for Cancer Treatment

“…[51] The antimicrobial Smp24 is a peptide derived from the venom of Scorpio maurus palmatus that has a 54 % homology with Pin 2 and has anticancer effects in acute leukemia (myeloid KG1-a) and lymphoid (CCRF-CEM) cells as well as in hepatoma (HepG2) and lung adenocarcinoma (A549) cells which may indicate that Pin2 also possesses anticancer activities. [52][53][54][55] To understand the importance and role of a specific amino acid sequence (ETFS) that is present in some peptides derived from the p53-MDM2 complex (these instigate cytotoxicity in cancer cell lines), eleven peptides were analyzed, where 4 peptides had amino acid exchanges and additions. With this, they observed that the exchange of isoleucine for a valine led to the formation of a smaller alpha-helix and that the addition of amino acids to the fragment (-ETFS-) favors intermolecular interactions, increasing the formation of hydrogen bridges, which leads to greater stability of alpha-helices.…”

1-Preparation, Characterization, and Efficiency of Loading Leiurus quinquestriatus Venom on Chitosan Nanoparticles Extracted from Some Scorpions .

“…Chitosan enjoys many benefits, especially while creating nanoparticles; among these, are its capacity to control the arrival of dynamic specialists, aversion to the utilization of dangerous natural solvents while manufacturing particles, its cationic nature, and its mucoadhesive person which increments remaining time at the site of ingestion (Islam, Bhuiyan and Islam, 2017). For insurance and prey catch, the venom apparatus of scorpions produce venom, which is a combination of proteins (synthetics and peptides) and non-proteins like inorganic salts, lipids, nucleotides, free amino acids, and water-based compounds (Gopalakrishnakone et al, 2015 andElrayess et al, 2022).…”

“…Most of the peptides in scorpion venom are disulfide and non-disulfide spread over, and a few of them have been displayed to have hostile to epileptic, hemolytic, against thrombotic, relieving, antibacterial, and anticancer properties (Elrayess et al, 2022;Mishal et al, 2013;Ortiz et al, 2015;Attarde and Pandit, 2016;Salem et al, 2016;Tobassum et al, 2018 ;Shah et al, 2018;Akef, 2019;Ahmadi et al, 2020;Díaz-García and Varela, 2020).…”