Yuan Zhu, Ningning Kang, Li Zhang, Jianju Tao, Wen Xue, Hui Li, Yingcan Li, Xucai Zheng, Wei He, Junting Ma
{"title":"利用 Erianin 靶向和降解食管鳞状细胞癌中的 OTUB1,实现抗转移。","authors":"Yuan Zhu, Ningning Kang, Li Zhang, Jianju Tao, Wen Xue, Hui Li, Yingcan Li, Xucai Zheng, Wei He, Junting Ma","doi":"10.1016/j.phymed.2024.155969","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Metastasis is a major contributor to mortality in patients with esophageal squamous cell carcinoma (ESCC); effective treatment is currently lacking. Erianin, a bioactive ingredient of traditional Chinese medicine, Dendrobium chrysotoxum, has anti-tumor activity against multiple human tumors. However, the effect and associated underlying mechanism of Erianin on ESCC antimetastasis remain unclear.</p><p><strong>Purpose: </strong>To investigate the anti-metastatic properties of Erianin in ESCC both in vitro and in vivo and associated molecular mechanisms.</p><p><strong>Methods: </strong>Wound healing assay, Transwell assay, CCK-8 assay, immunohistochemistry, and lung metastasis mouse model were carried out to examine ESCC cell migration and viability in vitro and in vivo. Drug affinity responsive target stability (DARTS), cellular thermal migration assay (CETSA), molecular docking, and Surface plasmon resonance (SPR) assay were used to confirm Erianin binding to ovarian tumor ubiquitin aldehyde-binding protein 1 (OTUB1) protein. Protein stability assay, cell transfection, and western blotting were used to confirm Erianin-mediated degradation of OTUB1 and Snail via the ubiquitin-proteasome pathway. qRT-PCR and western blotting were used to assess OTUB1expression in ESCC tissues.</p><p><strong>Results: </strong>Erianin suppressed the migration/invasion of ESCC cells without modulating cell viability in vitro and in vivo, bound to OTUB1 through DARTS, CETSA, and molecular docking, and SPR assay, and enhanced OTUB1 degradation via the ubiquitin-proteasome system. Moreover, Erianin inhibited the ESCC epithelial-mesenchymal transition by enhancing the ubiquitination and degradation of Snail via targeting OTUB1.</p><p><strong>Conclusion: </strong>Erianin inhibited ESCC metastasis through ubiquitination and degradation of Snail via targeting OTUB1. Our findings suggest Erianin as a novel OTUB1 inhibitor for preventing ESCC metastasis.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"135 ","pages":"155969"},"PeriodicalIF":6.7000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Targeting and degradation of OTUB1 by Erianin for antimetastasis in esophageal squamous cell carcinoma.\",\"authors\":\"Yuan Zhu, Ningning Kang, Li Zhang, Jianju Tao, Wen Xue, Hui Li, Yingcan Li, Xucai Zheng, Wei He, Junting Ma\",\"doi\":\"10.1016/j.phymed.2024.155969\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Metastasis is a major contributor to mortality in patients with esophageal squamous cell carcinoma (ESCC); effective treatment is currently lacking. Erianin, a bioactive ingredient of traditional Chinese medicine, Dendrobium chrysotoxum, has anti-tumor activity against multiple human tumors. However, the effect and associated underlying mechanism of Erianin on ESCC antimetastasis remain unclear.</p><p><strong>Purpose: </strong>To investigate the anti-metastatic properties of Erianin in ESCC both in vitro and in vivo and associated molecular mechanisms.</p><p><strong>Methods: </strong>Wound healing assay, Transwell assay, CCK-8 assay, immunohistochemistry, and lung metastasis mouse model were carried out to examine ESCC cell migration and viability in vitro and in vivo. Drug affinity responsive target stability (DARTS), cellular thermal migration assay (CETSA), molecular docking, and Surface plasmon resonance (SPR) assay were used to confirm Erianin binding to ovarian tumor ubiquitin aldehyde-binding protein 1 (OTUB1) protein. Protein stability assay, cell transfection, and western blotting were used to confirm Erianin-mediated degradation of OTUB1 and Snail via the ubiquitin-proteasome pathway. qRT-PCR and western blotting were used to assess OTUB1expression in ESCC tissues.</p><p><strong>Results: </strong>Erianin suppressed the migration/invasion of ESCC cells without modulating cell viability in vitro and in vivo, bound to OTUB1 through DARTS, CETSA, and molecular docking, and SPR assay, and enhanced OTUB1 degradation via the ubiquitin-proteasome system. Moreover, Erianin inhibited the ESCC epithelial-mesenchymal transition by enhancing the ubiquitination and degradation of Snail via targeting OTUB1.</p><p><strong>Conclusion: </strong>Erianin inhibited ESCC metastasis through ubiquitination and degradation of Snail via targeting OTUB1. Our findings suggest Erianin as a novel OTUB1 inhibitor for preventing ESCC metastasis.</p>\",\"PeriodicalId\":20212,\"journal\":{\"name\":\"Phytomedicine\",\"volume\":\"135 \",\"pages\":\"155969\"},\"PeriodicalIF\":6.7000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Phytomedicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.phymed.2024.155969\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/8/19 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Phytomedicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.phymed.2024.155969","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/19 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Targeting and degradation of OTUB1 by Erianin for antimetastasis in esophageal squamous cell carcinoma.
Background: Metastasis is a major contributor to mortality in patients with esophageal squamous cell carcinoma (ESCC); effective treatment is currently lacking. Erianin, a bioactive ingredient of traditional Chinese medicine, Dendrobium chrysotoxum, has anti-tumor activity against multiple human tumors. However, the effect and associated underlying mechanism of Erianin on ESCC antimetastasis remain unclear.
Purpose: To investigate the anti-metastatic properties of Erianin in ESCC both in vitro and in vivo and associated molecular mechanisms.
Methods: Wound healing assay, Transwell assay, CCK-8 assay, immunohistochemistry, and lung metastasis mouse model were carried out to examine ESCC cell migration and viability in vitro and in vivo. Drug affinity responsive target stability (DARTS), cellular thermal migration assay (CETSA), molecular docking, and Surface plasmon resonance (SPR) assay were used to confirm Erianin binding to ovarian tumor ubiquitin aldehyde-binding protein 1 (OTUB1) protein. Protein stability assay, cell transfection, and western blotting were used to confirm Erianin-mediated degradation of OTUB1 and Snail via the ubiquitin-proteasome pathway. qRT-PCR and western blotting were used to assess OTUB1expression in ESCC tissues.
Results: Erianin suppressed the migration/invasion of ESCC cells without modulating cell viability in vitro and in vivo, bound to OTUB1 through DARTS, CETSA, and molecular docking, and SPR assay, and enhanced OTUB1 degradation via the ubiquitin-proteasome system. Moreover, Erianin inhibited the ESCC epithelial-mesenchymal transition by enhancing the ubiquitination and degradation of Snail via targeting OTUB1.
Conclusion: Erianin inhibited ESCC metastasis through ubiquitination and degradation of Snail via targeting OTUB1. Our findings suggest Erianin as a novel OTUB1 inhibitor for preventing ESCC metastasis.
期刊介绍:
Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.