The Potent Antitumor Activity of Smp43 against Non-Small-Cell Lung Cancer A549 Cells via Inducing Membranolysis and Mitochondrial Dysfunction

Toxins (Basel). 2023 May 19;15(5):347. doi: 10.3390/toxins15050347.

Abstract

Research has been conducted to investigate the potential application of scorpion venom-derived peptides in cancer therapy. Smp43, a cationic antimicrobial peptide from Scorpio maurus palmatus venom, has been found to exhibit suppressive activity against the proliferation of multiple cancer cell lines. However, its impact on non-small-cell lung cancer (NSCLC) cell lines has not been previously investigated. This study aimed to determine the cytotoxicity of Smp43 towards various NSCLC cell lines, particularly A549 cells with an IC50 value of 2.58 μM. The results indicated that Smp43 was internalized into A549 cells through membranolysis and endocytosis, which caused cytoskeleton disorganization, a loss of mitochondrial membrane potential, an accumulation of reactive oxygen species (ROS), and abnormal apoptosis, cell cycle distribution, and autophagy due to mitochondrial dysfunction. Additionally, the study explored the in vivo protective effect of Smp43 in xenograft mice. The findings suggest that Smp43 has potential anticarcinoma properties exerted via the inducement of cellular processes related to cell membrane disruption and mitochondrial dysfunction.

Keywords: Smp43; anticancer; antimicrobial peptide; membranolysis; mitochondrial dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Antimicrobial Cationic Peptides / metabolism
  • Antimicrobial Cationic Peptides / pharmacology
  • Antimicrobial Cationic Peptides / therapeutic use
  • Apoptosis
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • Lung Neoplasms* / metabolism
  • Membrane Potential, Mitochondrial
  • Mice
  • Mitochondria / metabolism
  • Reactive Oxygen Species / metabolism

Substances

  • Antimicrobial Cationic Peptides
  • Reactive Oxygen Species

Grants and funding

This study was funded by the National Natural Science Foundation of China (no. 31861143050) and in part by the Academy of Scientific Research and Technology (ASRT, Egypt; China–Egypt Scientific and Technological Cooperation Program).