Cyanidin-3-O-glucoside inhibits the malignant progression of colorectal cancer by regulating Kruppel-like factor 4-mediated ERK/p38 signaling pathway

IF 3.3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicology and applied pharmacology Pub Date : 2025-02-17 DOI:10.1016/j.taap.2025.117268

Jian Chang, Geqiong Xiao

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引用次数: 0

Abstract

Background

Cyanidin-3-O-glucoside (Cy3g) is a natural anthocyanin, showing favorable anti-cancer efficacy in colorectal cancer (CRC). However, its specific mechanism in CRC remains largely unexplored.

Objective

This study aimed to investigate the underlying mechanisms of Cy3g on CRC.

Methods

Cell viability of human CRC cell lines (SW620, HT29, LS174T, and HCT116) and normal colon fibroblast cell line (CCD-18Co) treated with Cy3g was detected by CCK-8. Effects of Cy3g on malignant characteristics of SW620 cells were determined by CCK-8, EdU, colony formation, wound healing, Transwell, and flow cytometry assays. To further elucidate Cy3g's mechanism in CRC, KLF4 expression was detected by RT-qPCR, and expression of the extracellular signal-related kinase (ERK) and p38 was examined by western blotting. The effects and mechanisms of Cy3g on CRC progression were further validated in a xenograft mouse model.

Results

Cy3g significantly inhibited the cell viability of human CRC cell lines but rarely affected the cell viability of normal colon fibroblast. Cy3g dose-dependently inhibited proliferation, migration, and invasion and promoted apoptosis of SW620 cells. Moreover, Cy3g upregulated KLF4 expression and inactivated the ERK/p38 pathway in a concentration-dependent manner. KLF4 knockdown reversed the inhibitory effects of Cy3g on the malignant characteristics of SW620 and expression of ERK and p38. Animal experiments further validated that Cy3g inhibited tumor growth without altering body weight, activated KLF4, and suppressed the ERK/p38 pathway in CRC model mice.

Conclusion

Cy3g inhibits CRC progression by suppressing the KLF4-mediated ERK/p38 pathway, offering new insights into CRC prevention and treatment.

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来源期刊

Toxicology and applied pharmacology 医学-毒理学

CiteScore

6.80

自引率

2.60%

发文量

309

审稿时长

32 days

期刊介绍： Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products. Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged. Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.