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Clotrimazole (CTZ) is a wide-spectrum antifungal drug with antitumor activity. However, CTZ\u2019s effects on MM are unclear. We investigated CTZ\u2019s effect on MM cell proliferation and apoptosis induction mechanisms. CTZ\u2019s effects on MM.1S, NCI- H929, KMS-11, and U266 cell growth were investigated using Cell Counting Kit-8 (CCK-8) assay. The apoptotic cell percentage was quantified with annexin V-fluorescein isothiocyanate\/7-amino actinomycin D staining. Mitochondrial membrane potential (MMP) and cell cycle progression were evaluated. Reactive oxygen species (ROS) levels were measured via fluorescence microscopy. Expression of apoptosis-related and nuclear factor (NF)-\u03baB signaling proteins was analyzed using western blotting. The CCK-8 assay indicated that CTZ inhibited cell proliferation based on both dose and exposure time. Flow cytometry revealed that CTZ decreased apoptosis and MMP and induced G0\/G1 arrest. Immunofluorescence demonstrated that CTZ dose-dependently elevated in both total and mitochondrial ROS production. Western blotting showed that CTZ enhanced Bax and cleaved poly ADP-ribose polymerase and caspase-3 while decreasing Bcl-2, p-p65, and p-I\u03baB\u03b1. Therefore, CTZ inhibits MM cell proliferation by promoting ROS-mediated mitochondrial apoptosis, inducing G0\/G1 arrest, inhibiting the NF-\u03baB pathway, and has the potential for treating MM.<\/jats:p>","DOI":"10.1038\/s41598-024-66367-5","type":"journal-article","created":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T13:02:26Z","timestamp":1720098146000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Clotrimazole inhibits growth of multiple myeloma cells in vitro via G0\/G1 arrest and mitochondrial apoptosis"],"prefix":"10.1038","volume":"14","author":[{"given":"Yang","family":"Song","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Bo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuechun","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,4]]},"reference":[{"key":"66367_CR1","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1001\/jama.2022.0003","volume":"327","author":"AJ Cowan","year":"2022","unstructured":"Cowan, A. 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