2. Academic Validation
  3. Cytochrome P450 F3 promotes colorectal cancer via inhibiting NRF2-mediated ferroptosis

Cytochrome P450 F3 promotes colorectal cancer via inhibiting NRF2-mediated ferroptosis

  • Transl Oncol. 2024 Oct:48:102077. doi: 10.1016/j.tranon.2024.102077.
Ziyang Xu 1,  Cheng Xu 2,  Jie Lu 2,  Chenfeng He 3,  Xinyue Wang 4,  Dongfei Zhu 5,  Aizhong Wang 6,  Zhengyun Zhang 7,  Can Jiang 8
Affiliations

Affiliations

  • 1 The Department of Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Yishan Road 600, Shanghai 200233, China.
  • 2 The Department of Anesthesiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Yishan Road 600, Shanghai 200233, China.
  • 3 The Department of Integrative Bioanalytics, Aging and Cancer (IDAC), Institute of Development, Tohoku University, Sendai, Japan.
  • 4 The Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
  • 5 The Department of Cardiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 6 The Department of Anesthesiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Yishan Road 600, Shanghai 200233, China. Electronic address: wangaz@sjtu.edu.cn.
  • 7 The Department of Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Yishan Road 600, Shanghai 200233, China. Electronic address: zhengyunzhshjtu@126.com.
  • 8 The Department of Anesthesiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Yishan Road 600, Shanghai 200233, China. Electronic address: jiangcan1021@163.com.
PMID: 39106550 DOI: 10.1016/j.tranon.2024.102077
Abstract

Cytochrome P450 F3 (CYP4F3) is recognized as a disease-associated immune response initiator that is involved in the synthesis of Cholesterol, Steroids, and lipids. This study identified the upregulation of CYP4F3 expression in colorectal Cancer (CRC) and its association with poor patient prognosis through a comparative analysis between CRC tumor tissues with normal tissues from public databases. The overexpression of CYP4F3 in CT26.wt and SW620, promoted cell proliferation and migration, a reduction of cellular oxidative stress, an up-regulation of the oxidative stress-related pathway NRF2, and an inhibition of cellular Ferroptosis. Additionally, inhibition of NRF2 activity stimulated cellular Ferroptosis when CYP4F3 was overexpressed. Ferroptosis, characterized by iron-dependent lipid peroxidation, is a non-apoptotic way of cell death with a critical role in Cancer development. When given a Ferroptosis agonist to CYP4F3-overexpression CRC cells, NRF2 was activated, and cell proliferation and migration were reduced. Furthermore, the mice subcutaneously injected with CYP4F3-overexpression CT26.wt cells formed significantly larger tumors compared to the CYP4F3-vector CT26.wt cell group. This study systematically identified an important role of CYP4F3 in CRC development as a regulator of CRC cells to escape Ferroptosis via NRF2, highlighting the significance of CYP4F3 as a potential therapeutic target for CRC.

Keywords

CYP4F3; Colorectal cancer; Cytochrome P450; Ferroptosis; NRF2.

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