Cao Wei, Sun Mingyu, Yu K N, Zhao Lele, Feng Yue, Tan Chunhua, Yang Miaomiao, Wang Ying, Zhu Fengqin, Chen Lianjun, Nie Lili, Zhao Ye, Chen Guodong, Han Wei
Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, 230031, Hefei, P. R. China.
Teaching and Research Section of Nuclear Medicine, School of Basic Medical Sciences, Anhui Medical University, 230031, Hefei, P.R. China.
Cell Death Discov. 2024 Jan 23;10(1):42. doi: 10.1038/s41420-023-01743-0.
The gas therapy is drawing increasing attention in the treatment of many diseases including cancer. As one of gas signaling molecules, carbon monoxide (CO) has been proved to exert anti-cancer effects via triggering multiple cell death types, such as autophagy, apoptosis and necrosis. Here, we showed that low concentration CO delivered from CO-releasing molecule 3 (CORM-3) effectively induced ferroptosis, known as a novel proinflammatory programmed cell death, in vitro and in vivo. Mechanistically, we found that CO triggered ferroptosis by modulating the ROS/GSK3β/GPX4 signaling pathway, resulting in the accumulation of lipid hydroperoxides and the occurrence of ferroptosis. We think our findings provide novel insights into the anti-cancer mechanisms of CO, and suggest that CO could potentially be exploited as a novel ferroptosis inducer for cancer treatment in the future.
气体疗法在包括癌症在内的多种疾病治疗中日益受到关注。作为气体信号分子之一，一氧化碳（CO）已被证明可通过引发多种细胞死亡类型（如自噬、凋亡和坏死）发挥抗癌作用。在此，我们表明，从一氧化碳释放分子3（CORM-3）释放的低浓度CO在体外和体内均能有效诱导铁死亡，这是一种新型的促炎性程序性细胞死亡。从机制上讲，我们发现CO通过调节ROS/GSK3β/GPX4信号通路触发铁死亡，导致脂质氢过氧化物积累并发生铁死亡。我们认为我们的发现为CO的抗癌机制提供了新的见解，并表明CO未来有可能被开发为一种新型的癌症治疗铁死亡诱导剂。
