2. Academic Validation
  3. Cannabidiol mitigates radiation-induced intestine ferroptosis via facilitating the heterodimerization of RUNX3 with CBFβ thereby promoting transactivation of GPX4

Cannabidiol mitigates radiation-induced intestine ferroptosis via facilitating the heterodimerization of RUNX3 with CBFβ thereby promoting transactivation of GPX4

  • Free Radic Biol Med. 2024 Jun 1:222:288-303. doi: 10.1016/j.freeradbiomed.2024.05.047.
Congshu Huang 1,  Liangliang Zhang 2,  Pan Shen 3,  Zekun Wu 2,  Gaofu Li 3,  Yijian Huang 4,  Ting Ao 5,  Lin Luo 6,  Changkun Hu 7,  Ningning Wang 3,  Renzeng Quzhuo 8,  Lishan Tian 9,  Chaoji Huangfu 10,  Zebin Liao 11,  Yue Gao 12
Affiliations

Affiliations

  • 1 Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, 100850, China.
  • 2 College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
  • 3 Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, 100850, China.
  • 4 Senior Department of Orthopedics, The Fourth Medical Center of PLA General Hospital, Beijing, 100048, China.
  • 5 College of Pharmaceutical Science, Yunnan University of Chinese Medicine, Kunming, 650500, China.
  • 6 School of Nursing, Capital Medical University, Beijing, 100069, China.
  • 7 Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
  • 8 Department of General Internal Medicine, Naqu People's Hospital, Nagqu, Xizang Autonomous Region, 852007, China.
  • 9 Navy Qingdao Special Service Recuperation Center, Qingdao, 266071, China.
  • 10 Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, 100850, China. Electronic address: hfcj0370@foxmail.com.
  • 11 Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, 100850, China. Electronic address: 18701832213@163.com.
  • 12 Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, 100850, China. Electronic address: gaoyue@bmi.ac.cn.
PMID: 38830513 DOI: 10.1016/j.freeradbiomed.2024.05.047
Abstract

Radiation enteritis remains a major challenge for radiotherapy against abdominal and pelvic malignancies. Nevertheless, there is no approved effective therapy to alleviate irradiation (IR)-induced gastrointestinal (GI) toxicity. In the current study, Cannabidiol (CBD) was found to mitigate intestinal injury by GPX4-mediated Ferroptosis resistance upon IR exposure. RNA-sequencing was employed to investigate the underlying mechanism involved in the radio-protective effect of CBD, wherein runt-related transcription factor 3 (RUNX3) and its target genes were changed significantly. Further experiment showed that the transactivation of GPX4 triggered by the direct binding of RUNX3 to its promoter region, or by stimulating the transcriptional activity of NF-κB via RUNX3-mediated LILRB3 upregulation was critical for the anti-ferroptotic effect of CBD upon IR injury. Specially, CBD was demonstrated to be a molecular glue skeleton facilitating the heterodimerization of RUNX3 with its transcriptional chaperone core-biding factor β (CBFβ) thereby promoting their nuclear localization and the subsequent transactivation of GPX4 and LILRB3. In short, our study provides an alternative strategy to counteract IR-induced enteritis during the radiotherapy on abdominal/pelvic neoplasms.

Keywords

Cannabidiol; Ferroptosis; GPX4 transactivation; Heterodimerization with CBFβ; RUNX3; Radiation enteritis.

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