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

IF 2.7 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2025-02-28 DOI:10.1016/j.tice.2025.102793

Qiao Zhang , Zhijie Xu , Wanying Liu , Zhidong Cheng , Yating Ding , Yafeng Xie , Shengyu Yan

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引用次数: 0

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 (Fe^2 +), 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.

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来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.