{"title":"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。","authors":"Xue Li, Qiyan Li, Ying Huang, Heyang Zhou, Qianqing Yang, Lingmei Kong","doi":"10.1248/bpb.b25-00435","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 10","pages":"1485-1492"},"PeriodicalIF":1.7000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Quercetin, a Natural Dietary Flavonoid, Emerges a Novel USP7 Inhibitor with Anti-colorectal Cancer Effects.\",\"authors\":\"Xue Li, Qiyan Li, Ying Huang, Heyang Zhou, Qianqing Yang, Lingmei Kong\",\"doi\":\"10.1248/bpb.b25-00435\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":8955,\"journal\":{\"name\":\"Biological & pharmaceutical bulletin\",\"volume\":\"48 10\",\"pages\":\"1485-1492\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biological & pharmaceutical bulletin\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1248/bpb.b25-00435\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biological & pharmaceutical bulletin","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1248/bpb.b25-00435","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Quercetin, a Natural Dietary Flavonoid, Emerges a Novel USP7 Inhibitor with Anti-colorectal Cancer Effects.
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.
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.