Quercetin, a Natural Dietary Flavonoid, Emerges a Novel USP7 Inhibitor with Anti-colorectal Cancer Effects.

IF 1.7 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Xue Li, Qiyan Li, Ying Huang, Heyang Zhou, Qianqing Yang, Lingmei Kong
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Abstract

The human deubiquitinating enzyme ubiquitin-specific peptidase 7 (USP7) has emerged as a promising anti-tumor target, particularly in colorectal cancer, due to its regulation of the MDM2/p53 axis. Through a combination of ubiquitin C-terminal 7-amido-4-methylcoumarin hydrolysis assay and ubiquitin-propargylamide protease profiling, we identified the natural dietary flavonoid quercetin as a potent USP7 inhibitor in both cell-free and cellular contexts. Cellular thermal shift and surface plasmon resonance analyses demonstrated that quercetin is directly bound to USP7. Consistent with USP7 target engagement in cells, quercetin decreased MDM2 levels and subsequently increased the levels of p53. Moreover, quercetin also suppressed colorectal cancer cell proliferation by inducing G2/M cell cycle arrest and inhibiting cell migration. Collectively, our study identified quercetin as a novel and effective USP7 inhibitor with potent anti-colorectal cancer activity, highlighting its therapeutic potential for targeting the USP7-MDM2-p53 axis and warranting further exploration as a promising therapeutic agent in colorectal cancer treatment.

槲皮素,一种天然的膳食类黄酮,发现一种新的USP7抑制剂,具有抗结直肠癌的作用。
人类去泛素化酶泛素特异性肽酶7 (USP7)由于其调节MDM2/p53轴而成为一种有前景的抗肿瘤靶点,特别是在结直肠癌中。通过联合泛素c -末端7-氨基-4-甲基香豆素水解试验和泛素-丙炔酰胺蛋白酶分析,我们确定了天然膳食类黄酮槲皮素在细胞和细胞环境下都是一种有效的USP7抑制剂。细胞热移和表面等离子体共振分析表明槲皮素与USP7直接结合。与细胞中USP7靶点参与一致,槲皮素降低MDM2水平,随后增加p53水平。槲皮素还通过诱导G2/M细胞周期阻滞和抑制细胞迁移抑制结直肠癌细胞增殖。总之,我们的研究发现槲皮素是一种新型有效的USP7抑制剂,具有强大的抗结直肠癌活性,突出了其靶向USP7- mdm2 -p53轴的治疗潜力,值得进一步探索作为结直肠癌治疗的有前景的药物。
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来源期刊
CiteScore
3.50
自引率
5.00%
发文量
247
审稿时长
2 months
期刊介绍: Biological and Pharmaceutical Bulletin (Biol. Pharm. Bull.) began publication in 1978 as the Journal of Pharmacobio-Dynamics. It covers various biological topics in the pharmaceutical and health sciences. A fourth Society journal, the Journal of Health Science, was merged with Biol. Pharm. Bull. in 2012. The main aim of the Society’s journals is to advance the pharmaceutical sciences with research reports, information exchange, and high-quality discussion. The average review time for articles submitted to the journals is around one month for first decision. The complete texts of all of the Society’s journals can be freely accessed through J-STAGE. The Society’s editorial committee hopes that the content of its journals will be useful to your research, and also invites you to submit your own work to the journals.
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