AP2α Involved The Apoptosis Of Caspase-3 Pathway Aspirin Induced In Breast Cancer Cells

Substantial evidence indicates that aspirin and other non-steroidal anti-inflammatory drugs have antitumour activity against large bowel cancers. However, there are few reports about the chemopreventive role of these drugs in breast cancer. Here, induction of apoptosis and inhibition of proliferation were observed in MDA-MB-453 cells incubated with aspirin. Caspase-3 is required for some typical hallmarks of apoptosis, and is indispensable for apoptotic in all cell types examined. Aspirin can upregulate the activity of caspase-3, as well as its expression. Our previous study found that aspirin can inhibit ErbB2 to induce apoptosis. Further more, several reports indicated activating enhancer binding protein 2 alpha (AP2a) stimulates the transcription of the ErbB2 gene and correlates with apoptosis, leading us to hypothesize that AP2a is associated with apoptosis aspirin induced. Chromatin immunoprecipitation (ChIP) suggested that AP2a can straightforwardly bind to the PR(promoter region) of caspase-3. Additionally, luciferase analysis displayes AP2a is capable of inhibiting the luciferase activity of caspase-3. Loss and gain AP2a experiments illustrate the expression of caspase-3 declines in level of significance both at mRNA and protein level, so well as its activity. These data exhibit a correlation between caspase-3 activity and AP2a. We have further analysed the effect of aspirin on the expression of AP2a in breast cancer MDA-MB-453 cells.Here, we propose evidence that aspirin downregulates AP2a expression posttranscriptionally during apoptosis induced by aspirin. Aspirin treatment mediates the degradation of AP2a via proteosome-mediated pathway for the AP2a degradation blocked by MG132 in vivo. Consequently, we deduce that AP2a involved the apoptosis of caspase-3 pathway aspirin induced in breast cancer cells.