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Natural products, like the fungal metabolite neosetophomone B (NSP\u2010B), have emerged as potential therapeutic agents due to their bioactive properties. Our study investigated NSP\u2010B's antitumor effects on MM cell lines (U266 and RPMI8226) and the involved molecular mechanisms. NSP\u2010B demonstrated significant growth inhibition and apoptotic induction, triggered by reduced AKT activation and downregulation of the inhibitors of apoptotic proteins and S\u2010phase kinase protein. This was accompanied by an upregulation of p21Kip1 and p27Cip1 and an elevated Bax\/BCL2 ratio, culminating in caspase\u2010dependent apoptosis. Interestingly, NSP\u2010B also enhanced the cytotoxicity of bortezomib (BTZ), an existing MM treatment. Overall, our findings demonstrated that NSP\u2010B induces caspase\u2010dependent apoptosis, increases cell damage, and suppresses MM cell proliferation while improving the cytotoxic impact of BTZ. These findings suggest that NSP\u2010B can be used alone or in combination with other medicines to treat MM, highlighting its importance as a promising phytoconstituent in cancer therapy.<\/jats:p>","DOI":"10.1002\/cbin.12101","type":"journal-article","created":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T05:14:42Z","timestamp":1698383682000},"page":"190-200","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Neosetophomone B induces apoptosis in multiple myeloma cells via targeting of AKT\/SKP2 signaling pathway"],"prefix":"10.1002","volume":"48","author":[{"given":"Shilpa","family":"Kuttikrishnan","sequence":"first","affiliation":[{"name":"Translational Research Institute, Academic Health System Hamad Medical Corporation Doha Qatar"},{"name":"College of Pharmacy, QU Health Qatar University Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fareed","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Translational Research Institute, Academic Health System Hamad Medical Corporation Doha Qatar"},{"name":"Dermatology Institute, Academic Health System Hamad Medical Corporation Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jericha M.","family":"Mateo","sequence":"additional","affiliation":[{"name":"Translational Research Institute, Academic Health System Hamad Medical Corporation Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirti S.","family":"Prabhu","sequence":"additional","affiliation":[{"name":"Translational Research Institute, Academic Health System Hamad Medical Corporation Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamam","family":"El\u2010Elimat","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy Jordan University of Science and Technology Irbid Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas H.","family":"Oberlies","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of North Carolina at Greensboro Greensboro North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cedric J.","family":"Pearce","sequence":"additional","affiliation":[{"name":"Mycosynthetix Inc. 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