Curcumol promotes ferroptosis of colon cancer by targeting the ubiquitination and degradation of GPX4
GPX4 was upregulated in CC tissue and was correlated with poor survival of patients. Cur inhibited the proliferation of CC cells, accompanied by regulating Fe<sup>2+</sup> overload, reactive oxygen species (ROS) formation, malondialdehyde (MDA) production and superoxide dismutase (SOD) consumption. Furthermore, GPX4 was predicted and verified as the direct target of Cur by molecular docking and structure-based virtual prediction. Meanwhile, Cur could promote the ubiquitination-mediated degradation of GPX4, induce ferroptosis in CC cells and regulate the expression of ferroptosis-related protein FTH1 and TfR1. In addition, when GPX4 was overexpressed (GPX4-OE), the inhibitory effect of Cur on the expression of GPX4 and ferroptosis-related protein FTH1 and the promotion of TfR1 expression were abolished. Cur could inhibit CC by increasing the ubiquitination degradation level of GPX4 to induce ferroptosis in CC cells.
Authors
- Lianfang Liu
- Qiuying Yan
- Dongyang Xiang
- Dahai Hou (ORCID: https://orcid.org/0009-0001-8456-4334)
- Weixing Shen (ORCID: https://orcid.org/0000-0002-6454-3296)
- Liu Li (ORCID: https://orcid.org/0000-0002-9746-0067)
- Dongdong Sun (ORCID: https://orcid.org/0000-0003-1751-3884)
- Dongxin Tang
- Haibo Cheng (ORCID: https://orcid.org/0000-0003-3329-2225)
- Weiwei Tao (ORCID: https://orcid.org/0000-0002-5351-8693)
- Wuxia Zhao
Institutions
- Nanjing University of Chinese Medicine (CN)
Publication Details
- Journal
- Journal of Traditional and Complementary Medicine
- Published
- 2024-08-23
- DOI
- https://doi.org/10.1016/j.jtcme.2024.08.006
- Citations
- 6
- Primary Topic
- Ferroptosis and cancer prognosis
- Type
- article
- Field-Weighted Citation Impact
- 2.51
Funders
- National Natural Science Foundation of China
- Government of Jiangsu Province
- National Aerospace Science Foundation of China
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- Ministry of Higher Education, Science, Research and Innovation, Thailand
- “333 Project” of Jiangsu Province
- Key Project of Science and Technology Development of Nanjing Medicine
- Natural Science Research of Jiangsu Higher Education Institutions of China
- Funding Project for Academic Human Resources Development in Institutions of Higher Learning under the Jurisdiction of Beijing Municipality
- Foundation Research Project of Jiangsu Province