Yan Xi, Niu Yinghao, Wang Yaojie, Wei Sisi, Han Lina, Guo Zhongyu, Zhao Lianmei, Gao Feng
Department of Clinical Laboratory, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, China.
Department of Clinical Biobank, The First Hospital of Hebei Medical University, Shijiazhuang, 050031, China.
Open Med (Wars). 2025 Jan 15;20(1):20241100. doi: 10.1515/med-2024-1100. eCollection 2025.
This study aims to investigate the role and mechanism of -hydroxyl cinnamaldehyde (CMSP) in triggering ferroptosis of small cell lung cancer (SCLC) cells.
The impact of CMSP on ferroptosis in H1688 and SW1271 cells was assessed through cell experiments and biological information analysis. Moreover, the expression of heme oxygenase 1 (HMOX1) in SCLC tissue was examined.
Following CMSP treatment, a concentration-dependent increase in cell death was observed, and differentially expressed genes were found to be associated with ferroptosis. CMSP notably facilitated ferroptosis events, such as elevated levels of reactive oxygen species (ROS), Fe, malondialdehyde (MDA), transferrin receptor 1 (TFR1), divalent metal transporter 1 (DMT1), and decreased levels of glutathione (GSH), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4). Furthermore, CMSP promoted mitochondrial dysfunction, manifested as reduced mitochondrial volume, increased membrane density, elevated mitochondrial ROS, and decreased mitochondrial membrane potential. Consistently, the mitochondrial-targeted antioxidant Mito-TEMPO reversed CMSP-induced ferroptosis. Expression of the HMOX1 gene was markedly increased under CMSP treatment, while lower expression was observed in cancer tissue compared to adjacent tissue.
CMSP triggers mitochondrial dysfunction via HMOX1 activation, leading to ferroptosis in SCLC cells, underscoring its potential as a therapeutic agent for SCLC.
本研究旨在探讨对羟基肉桂醛（CMSP）在触发小细胞肺癌（SCLC）细胞铁死亡中的作用及机制。
通过细胞实验和生物信息分析评估CMSP对H1688和SW1271细胞铁死亡的影响。此外，检测SCLC组织中血红素加氧酶1（HMOX1）的表达。
CMSP处理后，观察到细胞死亡呈浓度依赖性增加，且发现差异表达基因与铁死亡相关。CMSP显著促进铁死亡事件，如活性氧（ROS）、铁、丙二醛（MDA）、转铁蛋白受体1（TFR1）、二价金属转运体1（DMT1）水平升高，而谷胱甘肽（GSH）、溶质载体家族7成员11（SLC7A11）和谷胱甘肽过氧化物酶4（GPX4）水平降低。此外，CMSP促进线粒体功能障碍，表现为线粒体体积减小、膜密度增加、线粒体ROS升高和线粒体膜电位降低。一致地，线粒体靶向抗氧化剂Mito-TEMPO可逆转CMSP诱导的铁死亡。CMSP处理下HMOX1基因的表达明显增加，而与癌旁组织相比，癌组织中的表达较低。
CMSP通过激活HMOX1触发线粒体功能障碍，导致SCLC细胞发生铁死亡，突显了其作为SCLC治疗药物的潜力。
