期刊
TOXINS
卷 14, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/toxins14090590
关键词
scorpion venom; antimicrobial peptides; Scorpio maurus palmatus; Smp24; A549; apoptosis; autophagy; necrosis; cell cycle arrest
资金
- Chinese National Natural Science Foundation [31861143050, 31772476, 31911530077, 82070038]
- Academy of Scientific Research and Technology (ASRT, Egypt)
- (China-Egypt Scientific and Technological Cooperation Program)
The antimicrobial peptide Smp24 has potential anti-lung cancer effects by targeting mitochondria and inducing apoptosis, autophagy, and cell cycle arrest through mitochondrial dysfunction and ROS accumulation.
Non-small cell lung cancer (NSCLC) is the leading cause of death in lung cancer due to its aggressiveness and rapid migration. The potent antitumor effect of Smp24, an antimicrobial peptide derived from Egyptian scorpion Scorpio maurus palmatus via damaging the membrane and cytoskeleton have been reported earlier. However, its effects on mitochondrial functions and ROS accumulation in human lung cancer cells remain unknown. In the current study, we discovered that Smp24 can interact with the cell membrane and be internalized into A549 cells via endocytosis, followed by targeting mitochondria and affect mitochondrial function, which significantly causes ROS overproduction, altering mitochondrial membrane potential and the expression of cell cycle distribution-related proteins, mitochondrial apoptotic pathway, MAPK, as well as PI3K/Akt/mTOR/FAK signaling pathways. In summary, the antitumor effect of Smp24 against A549 cells is related to the induction of apoptosis, autophagy plus cell cycle arrest via mitochondrial dysfunction, and ROS accumulation. Accordingly, our findings shed light on the anticancer mechanism of Smp24, which may contribute to its further development as a potential agent in the treatment of lung cancer cells.
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