2. Academic Validation
  3. Gastrodin promotes ferroptosis in CRC cells by inhibiting SKP2 to reduce NCOA4 ubiquitination

Gastrodin promotes ferroptosis in CRC cells by inhibiting SKP2 to reduce NCOA4 ubiquitination

  • Tissue Cell. 2025 Aug:95:102793. doi: 10.1016/j.tice.2025.102793.
Qiao Zhang 1,  Zhijie Xu 2,  Wanying Liu 3,  Zhidong Cheng 4,  Yating Ding 5,  Yafeng Xie 6,  Shengyu Yan 7
Affiliations

Affiliations

  • 1 Department of Proctology, the Second Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, China; Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China. Electronic address: zhangqiao0355@126.com.
  • 2 Department of Proctology, the Second Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, China; Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China. Electronic address: xuzhijie1035@126.com.
  • 3 Department of Proctology, the Second Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, China; Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China. Electronic address: liuwanying8932@126.com.
  • 4 Department of Proctology, the Second Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, China; Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China. Electronic address: chengzhidong2110@126.com.
  • 5 Department of Proctology, the Second Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, China; Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China. Electronic address: dingyating3215@aliyun.com.
  • 6 Department of Proctology, the Second Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, China; Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China. Electronic address: xieyafeng9321@88.com.
  • 7 Department of Proctology, the Second Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, China; Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China. Electronic address: shengyuyan8989@111.com.
PMID: 40048831 DOI: 10.1016/j.tice.2025.102793
Abstract

Background: Gastrodin, an important component of traditional Chinese medicine, is gaining interest because of its anti-tumor effects. Ferroptosis is a new mode of cell death, which has emerged as a promising target for colorectal Cancer (CRC) treatment. This research investigates the action mechanism of gastrodin on the process of CRC by inducing Ferroptosis.

Methods: The mRNA and protein levels were measured via qRT-PCR and western blot. Cell viability was assessed by CCK-8 assay. The cell proliferation was examined using colony formation assay. Live-Dead cell staining was evaluated by Calcein-AM/PI staining. The effect of Ferroptosis was evaluated by detecting the levels of Reactive Oxygen Species (ROS), intracellular total iron, ferrous iron (Fe2 +), malondialdehyde (MDA), glutathione (GSH) by kits, as well as the expressions of subunit solute carrier family 7 member 11 (SLC7A11), Glutathione Peroxidase 4 (GPX4), ferritin light chain (FTL) and acyl-CoA synthetase long chain family member 4 (ACSL4) by western blot. Co-immunoprecipitation (Co-IP) assay was applied to analyze the binding relationship between S-phase kinase-associated protein 2 (SKP2) and nuclear receptor coactivator 4 (NCOA4).

Results: Gastrodin could induce Ferroptosis in CRC cells. SKP2 ameliorated gastrodin induced Ferroptosis in CRC cells. Besides, SKP2 mediated NCOA4 degradation by ubiquitination. SKP2 was involved in Ferroptosis of CRC cells by regulating NCOA4. Gastrodin induced Ferroptosis in CRC cells via SKP2/NCOA4 axis.

Conclusion: Gastrodin repressed SKP2 expression, deactivated NCOA4 ubiquitination thus elevated NCOA4 expression, and promoted Ferroptosis in CRC cells.

Keywords

CRC; Ferroptosis; Gastrodin; NCOA4; SKP2; Ubiquitination.

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