蜂毒肽
A549电池
未折叠蛋白反应
程序性细胞死亡
内质网
细胞生物学
细胞凋亡
谷胱甘肽
化学
切碎
生物
生物化学
肽
酶
作者
Xuan Li,Sen Zhu,Zheng Li,Yuqi Meng,Sujie Huang,Qian Yu,Bin Li
标识
DOI:10.1080/10715762.2022.2131551
摘要
Melittin is a natural polypeptide present in bee venom, with significant anti-tumor activity. Melittin has been reported to induce cell death in lung carcinoma cell line A549 cells, suggesting an excellent potential for treating lung cancer. However, the core mechanism underlying melittin-induced cell death in A549 cells remains unclear. This work reports that melittin induces reactive oxygen species (ROS) burst, upregulates intracellular Fe2+ levels, disrupts the glutathione-glutathione peroxidase 4 antioxidant system, and increases lipid peroxide accumulation, eventually inducing cell death, indicating that ferroptosis may be involved in the antitumor effects of melittin in A549 cells. Furthermore, A549 cells treated with the ferroptosis inhibitors ferrostatin-1 and deferoxamine demonstrated that these inhibitors could reverse the cell death induced by melittin, further confirming that melittin induces A549 cell death via ferroptosis. Furthermore, the results also illustrated that melittin activated the endoplasmic reticulum (ER) stress-CHOP (C/EBP homologous protein) apoptotic signal, closely associated with high-level intracellular ROS. The ER stress inhibitor, 4-Phenylbutyric acid, was used to confirm that ER stress-CHOP apoptotic signaling is another molecular mechanism of melittin-induced A549 cell death. Thus, our results demonstrate that ferroptosis and ER stress-CHOP signaling are key molecular mechanisms of melittin-induced cell death in lung cancer.KEY POLICY HIGHLIGHTSMelittin upregulates intracellular Fe2+ levels, leading to the accumulation of lipid peroxides in A549 cells.Melittin disrupts the glutathione-glutathione peroxidase 4 antioxidant system in A549 cells.Melittin induces activation of endoplasmic reticulum stress-C/EBP homologous protein apoptosis signal.Ferroptosis and ER stress are the core molecular mechanisms underlying melittin-induced cell death in A549 cells.
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