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- Title
Exogenous carbon monoxide promotes GPX4-dependent ferroptosis through ROS/GSK3β axis in non-small cell lung cancer.
- Authors
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
- Abstract
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.
- Subjects
NON-small-cell lung carcinoma; CARBON monoxide; DEATH receptors; APOPTOSIS; CELL death
- Publication
Cell Death Discovery, 2024, Vol 10, Issue 1, p1
- ISSN
2058-7716
- Publication type
Article
- DOI
10.1038/s41420-023-01743-0