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• W2956337587 endingPage "1047" @default.
• W2956337587 startingPage "1038" @default.
• W2956337587 abstract "Triple negative breast cancer (TNBC) has very poor prognosis and no efficacious therapeutic options due to the absence of a validated molecular target. Therefore, novel therapeutic strategies against TNBC are urgently needed. Our team synthesized and screened a series of compounds derived from Rhein, of which 4F was selected for further analysis based on its ability to produce the vacuolated appearance of cells. Using Cell counting kit-8 assay, colony-formation assay, cell apoptosis and cell cycle assay, we compared the antitumor effects of 4F, Rhein and Cisplatin on a TNBC cell line MDA-MB-231 in vitro . The vacuoles in MDA-MB-231 cells were observed and analyzed by hematoxylin–eosin staining and transmission electron microscopy. Autophagy and apoptosis-related proteins including p62, Microtubule Light Chain 3 (LC3), Beclin-1 and Caspase-3 were determined by western blot. The tandem mRFP-GFP-LC3 Lentivirus was used for monitoring the maturation step of autophagosomes. Our data revealed that 4F had lower cytotoxicity to normal breast cell line MCF-10A as compared with positive drug Doxorubicin. Although 4F had better cytotoxicity than Rhein, it had no influence on cells apoptosis in 4F-treated cells. Accumulation of autolysosomes and autophagosomes was observed in 4F-treated MDA-MB-231 cells, accompanied by increased level of Beclin-1 protein. Enhanced autophagic flux was verified by higher ratio of LC3-II/LC3-I, the degradation of p62 protein and alteration in red and green fluorescence puncta. These findings suggested that the process of MDA-MB-231 cell death induced by 4F seemed rely mainly on autophagy rather than apoptosis. 4F may be an alternative drug candidate against TNBC and merits more exploration." @default.
• W2956337587 created "2019-07-23" @default.
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• W2956337587 date "2019-11-01" @default.
• W2956337587 modified "2023-09-23" @default.
• W2956337587 title "An autophagy-dependent cell death of MDA-MB-231 cells triggered by a novel Rhein derivative 4F" @default.
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• W2956337587 doi "https://doi.org/10.1097/cad.0000000000000820" @default.
• W2956337587 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31274517" @default.
• W2956337587 hasPublicationYear "2019" @default.
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