Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
Toxins (Basel). 2022 Oct 21;14(10):717. doi: 10.3390/toxins14100717.
Scorpion-venom-derived peptides have become a promising anticancer agent due to their cytotoxicity against tumor cells via multiple mechanisms. The suppressive effect of the cationic antimicrobial peptide Smp24, which is derived from the venom of , on the proliferation of the hepatoma cell line HepG2 has been reported earlier. However, its mode of action against HepG2 hepatoma cells remains unclear. In the current research, Smp24 was discovered to suppress the viability of HepG2 cells while having a minor effect on normal LO2 cells. Moreover, endocytosis and pore formation were demonstrated to be involved in the uptake of Smp24 into HepG2 cells, which subsequently interacted with the mitochondrial membrane and caused the decrease in its potential, cytoskeleton reorganization, ROS accumulation, mitochondrial dysfunction, and alteration of apoptosis- and autophagy-related signaling pathways. The protecting activity of Smp24 in the HepG2 xenograft mice model was also demonstrated. Therefore, our data suggest that the antitumor effect of Smp24 is closely related to the induction of cell apoptosis, cycle arrest, and autophagy via cell membrane disruption and mitochondrial dysfunction, suggesting a potential alternative in hepatocellular carcinoma treatment.
蝎毒素衍生肽因其通过多种机制对肿瘤细胞的细胞毒性而成为一种有前途的抗癌药物。阳离子抗菌肽 Smp24 来源于 的毒液，先前已有报道称其对肝癌细胞系 HepG2 的增殖具有抑制作用。然而，其对 HepG2 肝癌细胞的作用方式仍不清楚。在目前的研究中，发现 Smp24 抑制 HepG2 细胞的活力，而对正常 LO2 细胞的影响较小。此外，内吞作用和孔形成被证明参与了 Smp24 进入 HepG2 细胞的摄取，随后与线粒体膜相互作用，导致其电位降低、细胞骨架重组、ROS 积累、线粒体功能障碍以及改变凋亡和自噬相关信号通路。还证明了 Smp24 在 HepG2 异种移植小鼠模型中的保护活性。因此，我们的数据表明，Smp24 的抗肿瘤作用与通过细胞膜破坏和线粒体功能障碍诱导细胞凋亡、细胞周期停滞和自噬密切相关，这表明其在肝细胞癌治疗中具有潜在的替代作用。
