Discovery of vitexin as a novel VDR agonist that mitigates the transition from chronic intestinal inflammation to colorectal cancer

Sep 21, 2026

Uploaded by Miles

Colitis-associated colorectal cancer (CAC) arises in inflammatory bowel disease (IBD) after prolonged chronic inflammation, and preventing precancerous lesions while blocking progression remains a major research challenge. The study shows that loss of the Vitamin D receptor (VDR) accelerates transition from chronic colitis to colorectal cancer. Vitexin targets VDR, promotes nuclear translocation and transcriptional activity, and drives macrophage polarization toward M1 in a VDR-dependent manner.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages19

Reading Time48 min

AccessFree to download

Abstract

Key Findings

Mechanistic Evidence

In Vivo Validation

Chen et al. Molecular Cancer (2024) 23:196 Molecular Cancer [https://doi.org/10.1186/s12943-024-02108-6](https://doi.org/10.1186/s12943-024-02108-6) RESEARCH Open Access Discovery of vitexin as a novel VDR agonist that mitigates the transition from chronic intestinal inflammation to colorectal cancer Yonger Chen 1,2†, Jian Liang2†, Shuxian Chen3†, Nan Lin3, Shuoxi Xu2, Jindian Miao2, Jing Zhang2, Chen Chen2, Xin Yuan4, Zhuoya Xie5, Enlin Zhu6, Mingsheng Cai 1*, Xiaoli Wei5*, Shaozhen Hou2* and Hailin Tang5* Abstract Colitis-associated colorectal cancer (CAC) frequently develops in patients with inflammatory bowel disease (IBD) who have been exposed to a prolonged state of chronic inflammation. The investigation of pharmacological agents and their mechanisms to prevent precancerous lesions and inhibit their progression remains a significant focus and challenge in CAC research. Previous studies have demonstrated that vitexineffectively mitigates CAC, however, its precise mechanism of action warrants further exploration. This study reveals that the absence of the Vitamin D receptor ( VDR) accelerates the progression from chronic colitis to colorectal cancer. Our findings indicate that vitexin can specifically target the VDR protein, facilitating its translocation into the cell nucleus to exert transcriptional activity. Additionally, through a co-culture model of macrophages and cancer cells, we observed that vitexin promotes the polarization of macrophages towards the M1 phenotype, a process that is dependent on VDR. Furthermore, ChIP-seq analysis revealed that vitexin regulates the transcriptional activation of phenazine biosynthesis-like domain protein (PBLD) via VDR. ChIP assays and dual luciferase reporter assays were employed to identify the functional PBLD regulatory region, confirming that the VDR/PBLD pathway is critical for vitexin-mediated regulation of macrophage polarization. Finally, in a mouse model with myeloid VDR gene knockout, we found that the protective effects of vitexin were abolished in mid-stage CAC. In summary, our study establishes that vitexin targets VDR and modulates macrophage polarization through the VDR/PBLD pathway, thereby alleviating the transition from chronic colitis to colorectal cancer. †Yonger Chen, Jian Liang and Shuxian Chen contributed equally to this work. *Correspondence: Mingsheng Cai[caimingsheng@gzhmu.edu.cn](caimingsheng@gzhmu.edu.cn)[ ](caimingsheng@gzhmu.edu.cn)Xiaoli Wei [weixl@sysucc.org.cn](weixl@sysucc.org.cn)[ ](weixl@sysucc.org.cn)Shaozhen Hou [hsz0214@gzucm.edu.cn](hsz0214@gzucm.edu.cn)[ ](hsz0214@gzucm.edu.cn)Hailin Tang [tanghl@sysucc.org.cn](tanghl@sysucc.org.cn) Full list of author information is available at the end of the article © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://](http://)[ ](http://)[creativecommons.org/l](creativecommons.org/l)icenses/by-nc-nd/4.0/. Highlights • Deficiency in VDR accelerates the progression from chronic colitis to colorectal cancer. • Vitexin regulates transcription

FAQs

What is the main focus of the study?

The study investigates how vitexin functions as a novel VDR agonist to mitigate the transition from chronic intestinal inflammation to colorectal cancer.

What role does VDR play in the progression from chronic colitis to colorectal cancer?

The findings indicate that absence of VDR accelerates progression from chronic colitis to colorectal cancer.

How does vitexin affect macrophages in the tumor microenvironment?

Vitexin promotes macrophage polarization toward the M1 phenotype, and this effect depends on VDR.

Sep 21, 2026

Uploaded by Miles