Magnolol 对野生型 p53 和肠道微生物群的双重靶向作用可抑制关键的代谢过程并杀死 CRC 细胞。

IF 6.1 2区 医学 Q1 CHEMISTRY, MEDICINAL
Phytotherapy Research Pub Date : 2024-10-01 Epub Date: 2023-06-16 DOI:10.1002/ptr.7924
Haixia Ji, Ou Qiao, Yi Zhang, Wenzhe Wang, Xiaoyin Han, Xinyu Zhang, Changxiao Liu, Wenyuan Gao
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引用次数: 0

摘要

癌细胞消耗大量葡萄糖,并主要利用糖酵解产生 ATP。这种新陈代谢特征(沃伯格效应)使癌细胞能够将葡萄糖导入生物合成,以支持和维持其急剧的生长和增殖。目前,我们对沃伯格效应的代谢和机理影响及其与生物合成的关系仍不清楚。在此,我们说明了肿瘤抑制因子 p53 介导的马格诺洛尔(MAG)会引发结肠癌细胞凋亡。并且,MAG 通过转录调节其下游基因 TP53 诱导的糖酵解调节因子和细胞色素 c 氧化酶的生物合成,调节糖酵解和氧化磷酸化步骤,抑制体内和体外的细胞增殖和肿瘤生长。同时,我们发现 MAG 与其自身肠道微生物区系的特征代谢物协同抑制肿瘤,尤其是显著降低犬尿氨酸(Kyn)/色氨酸(Trp)的比例。此外,我们还探讨了影响 MAG 的基因、微生物群和代谢物之间的密切关系。因此,我们确定了 p53-微生物群-代谢物的作用机制,该机制可用于治疗代谢引起的结直肠癌,特别是 MAG 可作为治疗结直肠癌的候选药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Dual targeting of wild-type p53 and gut microbiota by Magnolol represses key metabolic process and kills CRC cells.

Cancer cells consume considerable glucose quantities and majorly employ glycolysis for ATP generation. This metabolic signature (the Warburg effect) allows cancer cells to channel glucose to biosynthesis to support and maintain their dramatic growth along with proliferation. Currently, our understanding of the metabolic and mechanistic implications of the Warburg effect along with its relationship with biosynthesis remains unclear. Herein, we illustrate that the tumor repressor p53 mediate Magnolol (MAG) triggers colon cancer cell apoptosis. And MAG regulates the glycolytic and oxidative phosphorylation steps through transcriptional modulation of its downstream genes TP53-induced glycolysis modulator and biosynthesis of cytochrome c oxidase, attenuating cell proliferation and tumor growth in vivo and in vitro. Meanwhile, we show that MAG cooperates with its own intestinal microflora characteristic metabolites to repress tumors, especially remarkably declined kynurenine (Kyn)/tryptophan (Trp) ratio. Besides, strong relationships of MAG influenced genes, microbiota, as well as metabolites, were explored. Therefore, we established that p53-microbiota-metabolites function as a mechanism, which enable therapy approaches against metabolism-implicated colorectal cancer, in particular MAG as a prospective candidate for treating colorectal cancer.

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来源期刊
Phytotherapy Research
Phytotherapy Research 医学-药学
CiteScore
12.80
自引率
5.60%
发文量
325
审稿时长
2.6 months
期刊介绍: Phytotherapy Research is an internationally recognized pharmacological journal that serves as a trailblazing resource for biochemists, pharmacologists, and toxicologists. We strive to disseminate groundbreaking research on medicinal plants, pushing the boundaries of knowledge and understanding in this field. Our primary focus areas encompass pharmacology, toxicology, and the clinical applications of herbs and natural products in medicine. We actively encourage submissions on the effects of commonly consumed food ingredients and standardized plant extracts. We welcome a range of contributions including original research papers, review articles, and letters. By providing a platform for the latest developments and discoveries in phytotherapy, we aim to support the advancement of scientific knowledge and contribute to the improvement of modern medicine.
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