Scorpion Peptide Smp24 Exhibits a Potent Antitumor Effect on Human Lung Cancer Cells by Damaging the Membrane and Cytoskeleton In Vivo and In Vitro

Abstract

Smp24, a cationic antimicrobial peptide identified from the venom gland of the Egyptian scorpion Scorpio maurus palmatus, shows variable cytotoxicity on various tumor (KG1a, CCRF-CEM and HepG2) and non-tumor (CD34+, HRECs, HACAT) cell lines. However, the effects of Smp24 and its mode of action on lung cancer cell lines remain unknown. Herein, the effect of Smp24 on the viability, membrane disruption, cytoskeleton, migration and invasion, and MMP-2/-9 and TIMP-1/-2 expression of human lung cancer cells have been evaluated. In addition, its in vivo antitumor role and acute toxicity were also assessed. In our study, Smp24 was found to suppress the growth of A549, H3122, PC-9, and H460 with IC50 values from about 4.06 to 7.07 µM and show low toxicity to normal cells (MRC-5) with 14.68 µM of IC50. Furthermore, Smp24 could induce necrosis of A549 cells via destroying the integrity of the cell membrane and mitochondrial and nuclear membranes. Additionally, Smp24 suppressed cell motility by damaging the cytoskeleton and altering MMP-2/-9 and TIMP-1/-2 expression. Finally, Smp24 showed effective anticancer protection in a A549 xenograft mice model and low acute toxicity. Overall, these findings indicate that Smp24 significantly exerts an antitumor effect due to its induction of membrane defects and cytoskeleton disruption. Accordingly, our findings will open an avenue for developing scorpion venom peptides into chemotherapeutic agents targeting lung cancer cells.

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

“…Despite the effectiveness and selectivity against tumor cells in vitro experiments, the use of peptide-based anticancer agents in clinical trials is still a challenge due to the degradation by proteases in vivo [ 54 ]. Our animal experiments revealed that 2 mg/kg Smp24 treatment leads to a significant decrease in tumor weight and volume, while it does not cause notable changes in body weight and important organs, which is consistent with the previous study [ 10 , 11 ], indicating the considerable stability and high selectivity of Smp24 against tumor tissues in vivo ( Figure 9 ). Thus, Smp24 is an ideal antitumor candidate molecule.…”

“…We also revealed that Smp24 significantly suppresses the proliferation of HepG2 cells, while having a slight effect on that of the normal hepatic cell LO2, suggesting a highly selective activity against tumor cells ( Figure 1 A). It is noteworthy that the IC 50 values of Smp24 against HepG2 cells was slightly higher than the results in our previous study against A549 cells [ 10 , 11 ]. Therefore, there are some common mechanisms against two kinds of tumor by Smp24.…”

“…In line with this, the reorganization of F-actin in the HepG2 cell cytoskeleton was observed in the presence of Smp24 ( Figure 3 ). However, contrary to its effects on A549 cells [ 10 , 11 ], Smp24 could not inhibit the mobility of HepG2 cells in the wound-healing and transwell assays (data not shown). Therefore, there are some discrepancies in its mechanism against two cell lines and further research is necessary.…”

“…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.…”

Effect of Silkworm Pupa Protein Hydrolysates on Proliferation of Gastric Cancer Cells In Vitro

“…For the study of the cytoskeleton, we mainly analyzed the root cause of cytoskeleton collapse in morphology. Because actin is a structural protein of microfilaments and a major cytoskeletal protein, it plays an important role in many subcellular processes, such as cytoplasmic flow, organelle and nuclear localization, cell morphogenesis and cell division [ 36 ]. Similarly, microtubules, as a polar cytoskeleton, mainly play a role in maintaining cell morphology and assisting intracellular transport, and can be assembled with other proteins into spindles, grana, centrioles, flagella, ciliated neural tubes and other structures [ 37 , 38 ].…”