Title: Molecular mechanism of aspirin-induced apoptosis in neuroblastoma cells
Abstract: Objective To investigate the apoptotic effect and the underlying mechanism of aspirin on neuroblastoma cells.Methods Neuroblastoma SH-SY5Y and CHLA-119 cell lines were treated with aspirin.Cell proliferation inhibition was examined by methyl thiazol tetrazolium (MTT) assay.Cell death was detected by trypan blue exclusion assay.Apoptosis was examined by Annexin V staining and flow cytometry assay.Activation of Caspase-9/-3' poly adenosine diphosphate-ribose polymerase (PARP) cleavage and the expression of B cell lymphoma/leukemia-2 (bcl-2),bcl-xL,myeloid cell leukemia-1 (Mcl-1) were analyzed by Western blotting.Results Aspirin had potent antiproliferative and cell killing effect in neuroblastoma cells.After treatment for 72 h,aspirin achieved 50% inhibitory dose (IC50) 4.8 mmol/L and 4.6 mmol/L in SH-SY5Y and CHLA-119 cell lines,respectively.After treatment for 48 h,aspirin induced 45% and 46% cells undergoing cell death in SH-SY5Y and CHLA-119 cell lines,respectively.Flow cytometery assay showed that after treatment for 24 h,aspirin induced 46% and 42% cells undergoing apoptosis in SH-SY5Y and CHLA-119 cell lines,respectively.Furthermore,Western blotting analysis showed that after treatment for 24 h,aspirin triggered activation of Caspases-9/-3 ' cleavage of PARP,as well as down-regulation of bcl-xL and Mcl-1 in both SH-SY5Y and CHLA-119 cell lines.Conclusion Aspirin can potently activate apoptosis signaling through suppressing the expression of bcl-xL and Mcl-l in neuroblastoma cells,which leads to strong anti-neuroblastoma activity.
Key words:
Aspirin; Neuroblastoma; B cell lymphoma/leukemia-xL; Myeloid cell leukemia-1
Publication Year: 2014
Publication Date: 2014-10-08
Language: en
Type: article
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