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The transcriptional repressor B-cell lymphoma 6 (BCL6) is indispensable for GC formation and contributes to lymphomagenesis via its BTB domain-mediated suppression of target genes. Dysregulation of BCL6 underpins the pathogenesis of GC-derived NHL. While pharmacological targeting the BCL6-BTB domain has shown therapeutic promise, natural product-based inhibitors remain underexplored. In this study, resveratrol, a polyphenolic compound derived from grapes, was identified as a potent BCL6 inhibitor through a comprehensive screen of traditional Chinese medicine monomers using Homogeneous Time-Resolved Fluorescence (HTRF) assay. As a BCL6 natural inhibitor, resveratrol effectively disrupted the BCL6\/SMRT interaction, reactivated suppressed gene expression, and inhibited the proliferation of GC-derived NHL cells. It also exhibited synergistic efficacy when combined with EZH2 and PRMT5 inhibitors. In vivo, resveratrol suppressed GC formation, reduced follicular helper T-cell frequencies, impaired class-switch recombination, and disrupted immunoglobulin affinity maturation. Furthermore, it markedly inhibited the progression of GC-derived NHL in animal models. Our findings demonstrate that resveratrol functions as a natural BCL6 inhibitor with significant therapeutic potential for the treatment of GC-derived NHL.<\/jats:p>\n          <jats:p>\n            <jats:bold>Graphical abstract<\/jats:bold>\n          <\/jats:p>","DOI":"10.1007\/s11418-024-01873-4","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T20:24:14Z","timestamp":1736972654000},"page":"399-411","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Resveratrol as a BCL6 natural inhibitor suppresses germinal center derived Non-Hodgkin lymphoma cells growth"],"prefix":"10.1007","volume":"79","author":[{"given":"Yajing","family":"Xing","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunbin","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhoujiang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guixue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7165-0014","authenticated-orcid":false,"given":"Yadong","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"key":"1873_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A (2024) Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 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