{"id":1182,"date":"2024-09-30T09:06:10","date_gmt":"2024-09-30T09:06:10","guid":{"rendered":"https:\/\/amm-journal.org\/?p=1182"},"modified":"2024-09-30T09:06:35","modified_gmt":"2024-09-30T09:06:35","slug":"brusatol-increases-chemotherapeutic-drug-efficacy-in-pancreatic-ductal-adenocarcinoma-by-suppressing-nrf2-signaling","status":"publish","type":"post","link":"https:\/\/amm-journal.org\/index.php\/2024\/09\/30\/brusatol-increases-chemotherapeutic-drug-efficacy-in-pancreatic-ductal-adenocarcinoma-by-suppressing-nrf2-signaling\/","title":{"rendered":"Brusatol increases chemotherapeutic drug efficacy in pancreatic ductal adenocarcinoma by suppressing Nrf2 signaling"},"content":{"rendered":"<p>Announcing a new publication for <em>Acta Materia Medica<\/em> journal. \u00a0Chemoresistance to gemcitabine (Gem) remains a substantial obstacle in the treatment of pancreatic ductal adenocarcinoma carcinoma (PDAC). Nrf2, a transcription factor responsive to oxidative stress, has been implicated as a key contributor to chemoresistance. Previous studies have demonstrated anti-tumor effects of brusatol (BRT) in PDAC. Herein, we aimed to investigate the efficacy of BRT in enhancing chemosensitivity to Gem and to elucidate the underlying mechanisms involving Nrf2. Gain- and-loss-of-function experiments revealed that Nrf2 exacerbated Gem chemoresistance in PDAC cells. Additionally, BRT effectively inhibited PDAC cell proliferation and enhanced Gem chemosensitivity. Mechanistic investigations demonstrated that BRT sensitized PDAC cells to Gem by suppressing Nrf2 at the transcriptional level. Activation of Nrf2 conteracted BRT\u2019s effects on chemosensitivity. In contrast, combination treatment with Nrf2 silencing and BRT demonstrated a more potent inhibitory effect on Gem\u00a0<em>in vitro<\/em>\u00a0and\u00a0<em>in vivo<\/em>, thereby indicating the Nrf2 dependence of BRT action. These findings highlight BRT\u2019s ability to enhance Gem chemosensitivity by inhibiting Nrf2 signaling in PDAC; therefore, BRT may serve as a potential adjuvant therapy for PDAC.<\/p>\n<p><a href=\"https:\/\/www.scienceopen.com\/hosted-document?doi=10.15212\/AMM-2024-0016\">https:\/\/www.scienceopen.com\/hosted-document?doi=10.15212\/AMM-2024-0016<\/a><\/p>\n<p><em>Acta Materia Medica<\/em> welcomes the submission of research articles, review articles, databases, mini reviews, commentaries, editorials, short communications, case report articles and study protocols.<\/p>\n<p><strong>Submission Process<\/strong><\/p>\n<p>Submissions <em>to Acta Materia Medica<\/em> are made using ScholarOne, the online submission and peer review system. Registration and access are available at <a href=\"https:\/\/mc04.manuscriptcentral.com\/ammed\">https:\/\/mc04.manuscriptcentral.com\/ammed<\/a><\/p>\n<p>Queries about the journal can be sent to editorialoffice@amm-journal.org.<\/p>\n<p>Please visit <a href=\"https:\/\/amm-journal.org\/\">https:\/\/amm-journal.org\/<\/a> to learn more about the journal.<\/p>\n<p><strong>Editorial Board:<\/strong> <a href=\"https:\/\/amm-journal.org\/index.php\/editorial-board\/\">https:\/\/amm-journal.org\/index.php\/editorial-board\/<\/a><\/p>\n<p>There are no author submission or article processing fees.<\/p>\n<p>Follow <strong><em>Acta Materia Medica <\/em><\/strong>on Twitter <a href=\"https:\/\/twitter.com\/AMM_journal\">https:\/\/twitter.com\/AMM_journal<\/a>; <a href=\"https:\/\/www.facebook.com\/Zoonoses-Journal-100462755574114\">Facebook<\/a> (<a href=\"https:\/\/www.facebook.com\/AMMjournal\">https:\/\/www.facebook.com\/AMMjournal<\/a>)<\/p>\n<p><strong>eISSN <\/strong>2737-7946<\/p>\n<p>Juan Zhang, Hongxi Xu and Yulin Wu et al. Brusatol increases chemotherapeutic drug efficacy in pancreatic ductal adenocarcinoma by suppressing Nrf2 signaling.\u00a0<em>Acta Materia Medica.\u00a0<\/em>2024. Vol. 3(3):312-327. DOI: 10.15212\/AMM-2024-0016<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Announcing a new publication for Acta Materia Medica journal. \u00a0Chemoresistance to gemcitabine (Gem) remains a substantial obstacle in the treatment of pancreatic ductal adenocarcinoma carcinoma (PDAC). Nrf2, a transcription factor responsive to oxidative stress, has been implicated as a key contributor to chemoresistance. Previous studies have demonstrated anti-tumor effects of brusatol (BRT) in PDAC. Herein, [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[2],"tags":[323,78,322,324],"class_list":["post-1182","post","type-post","status-publish","format-standard","hentry","category-news-and-events","tag-brt","tag-brusatol","tag-gemcitabine","tag-pdac-cell-proliferation"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Brusatol increases chemotherapeutic drug efficacy in pancreatic ductal adenocarcinoma by suppressing Nrf2 signaling - AMM Journal<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/amm-journal.org\/index.php\/2024\/09\/30\/brusatol-increases-chemotherapeutic-drug-efficacy-in-pancreatic-ductal-adenocarcinoma-by-suppressing-nrf2-signaling\/\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Brusatol increases chemotherapeutic drug efficacy in pancreatic ductal adenocarcinoma by suppressing Nrf2 signaling - AMM Journal\" \/>\n<meta property=\"og:description\" content=\"Announcing a new publication for Acta Materia Medica journal. \u00a0Chemoresistance to gemcitabine (Gem) remains a substantial obstacle in the treatment of pancreatic ductal adenocarcinoma carcinoma (PDAC). Nrf2, a transcription factor responsive to oxidative stress, has been implicated as a key contributor to chemoresistance. Previous studies have demonstrated anti-tumor effects of brusatol (BRT) in PDAC. 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