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Glaucocalyxin A (GLA), a natural bioactive product derived from the <jats:italic>Rabdosia rubescens<\/jats:italic> plant, has strong anticancer activity. In this study, the effect and molecular mechanism of GLA on imatinib\u2010sensitive and imatinib\u2010resistant CML cells harboring T315I mutation via a combined deconvolution strategy of chemoproteomics and label\u2010free proteomics is investigated. The data demonstrated that GLA restrains proliferation and induces mitochondria\u2010dependent apoptosis in both imatinib\u2010sensitive and resistant CML cells. GLA covalently binds to the cysteine residues of mitochondrial voltage\u2010dependent anion channels (VDACs), resulting in mitochondrial damage and overflow of intracellular apoptotic factors, eventually leading to apoptosis. In addition, the combination of GLA with elastin, a mitochondrial channel VDAC2\/3 inhibitor, enhances mitochondria\u2010dependent apoptosis in imatinib\u2010sensitive and \u2010resistant CML cells, representing a promising therapeutic approach for leukemia treatment. Taken together, the results show that GLA induces mitochondria\u2010dependent apoptosis via covalently targeting VDACs in CML cells. GLA may thus be a candidate compound for the treatment of leukemia.<\/jats:p>","DOI":"10.1002\/adbi.202300538","type":"journal-article","created":{"date-parts":[[2023,12,17]],"date-time":"2023-12-17T23:20:23Z","timestamp":1702855223000},"source":"Crossref","is-referenced-by-count":7,"title":["Chemoproteomics Reveals Glaucocalyxin A Induces Mitochondria\u2010Dependent Apoptosis of Leukemia Cells via Covalently Binding to VDAC1"],"prefix":"10.1002","volume":"8","author":[{"given":"Yehai","family":"An","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences and School of Traditional Chinese Medicine Southern Medical University  Guangzhou 510515 China"},{"name":"State Key Laboratory of Organ Failure Research Guangdong Provincial Key Laboratory of Viral Hepatitis Research Department of Infectious Diseases Nanfang Hospital Southern Medical University  Guangzhou 510515 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