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Non-small-cell lung carcinoma (NSCLC) continues to be a vital disease worldwide for its high incidence and consequent mortality rate. In this study, we investigated the anti-cancer effect of LZ-101, a new derivative of danofloxacin, against non-small-cell lung cancer and the underlying mechanisms. In vitro, LZ-101 inhibited the viability of human non-small cell lung cancer cell lines. We demonstrated that LZ-101 induced mitochondrial-mediated apoptosis by increasing Bax/Bcl-2 ratio, loss of mitochondrial membrane potential (ΔΨm), release of cytochrome c (Cyt c) and apoptosis-inducing factor (AIF) in A549 cells. Further research illuminated that LZ-101 induced apoptosis was related to the activation of FOXO3a/Bim pathway. Moreover, we found that LZ-101 increased the stability of FOXO3a by blocking autophagy-dependent FOXO3a degradation. However, inhibition of autophagosome formation abolished FOXO3a stabilization and apoptosis induced by LZ-101. In vivo, LZ-101 exerted a remarkable anti-tumor activity with high safety in xenograft model inoculated A549 tumor through the same mechanism as in our in vitro study. In conclusion, our findings indicated that LZ-101 induces mitochondrial apoptosis and stabilizes FOXO3a by blocking autophagy flux.
Pubmed ID: 31217472
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Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentionsPrivately held company that develops and produces antibodies, ELISA kits, ChIP kits, proteomic kits, and other related reagents used to study cell signaling pathways that impact human health.
View all literature mentionsCommercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.
View all literature mentionsA commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.
View all literature mentionsCell line NCI-H460 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line A-549 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H1299 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionslaboratory mouse with name BALB/cAnNCrl from MGI.
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