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• W1567252384 abstract "Background and Purpose 4‐[3,5‐Bis(2‐chlorobenzylidene)‐4‐oxo‐piperidine‐1‐yl]‐4‐oxo‐2‐butenoic acid CLEFMA is a new anti‐cancer molecule. Here, we investigated changes in apoptosis and inflammatory markers during CLEFMA ‐induced tumour suppression. Experimental Approach Lung adenocarcinoma H441 and A549 , and normal lung fibroblast CCL151 cell lines were used, along with a xenograft model of H441 cells implanted in mice. Tumour tissues were analysed by immunoblotting, immunohistochemistry and/or biochemical assays. The ex vivo results were confirmed by performing selected assays in cultured cells. Key Results CLEFMA ‐induced cell death was associated with cleavage of caspases 3/9 and PARP . In vivo, CLEFMA treatment resulted in a dose‐dependent suppression of tumour growth and 18 F ‐fluorodeoxyglucose uptake in tumours, along with a reduction in the expression of the proliferation marker Ki ‐67. In tumour tissue homogenates, the anti‐apoptotic markers (cellular inhibitor of apoptosis protein‐1( cIAP1 ), Bcl ‐xL, Bcl ‐2, and survivin) were inhibited and the pro‐apoptotic Bax and BID were up‐regulated. Further, CLEFMA decreased translocation of phospho‐p65– NF ‐κ B into the nucleus. In vitro , it inhibited the DNA ‐binding and transcriptional activity of NF ‐κ B . It also reduced the expression of COX ‐2 in tumours and significantly depressed serum TNF ‐α and IL ‐6 levels. These effects of CLEFMA were accompanied by a reduced transcription and/or translation of the invasion markers VEGF , MMP9 , MMP10 , Cyclin D1 and ICAM‐1 . Conclusions and Implications Overall, CLEFMA inhibited growth of lung cancer xenografts and this tumour suppression was associated with NF ‐κ B ‐regulated anti‐inflammatory and anti‐metastatic effects." @default.
• W1567252384 created "2016-06-24" @default.
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• W1567252384 date "2013-11-14" @default.
• W1567252384 modified "2023-09-25" @default.
• W1567252384 title "Preclinical evaluation of 4-[3,5-bis(2-chlorobenzylidene)-4-oxo-piperidine-1-yl]-4-oxo-2-butenoic acid, in a mouse model of lung cancer xenograft" @default.
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• W1567252384 doi "https://doi.org/10.1111/bph.12406" @default.
• W1567252384 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3838689" @default.
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