Oxidative stress induces apoptosis of MCF7 cells treated by HDAC inhibitors (655.13)

When MCF7 human breast adenocarcinoma cells were treated by HDAC inhibitors (HDACi), SAHA or THS79-12, considerable portions of MCF7 cells became floated and underwent apoptosis. While annexin A1 was induced in both floated and attached cells, this protein in floated cells was mono-ubiquitinated as determined by Western blots, suggesting that DNA damage took place. PML, a protein that plays an important role in DNA damage induced apoptosis was acetylated, and Bclxs was induced, and caspase 3 was cleaved, demonstrating features of apoptosis. 8-Oxoguanosine contents of cells treated with HDAC inhibitors increased by 8 folds in floating cells as compared with those in attached cells. These apoptotic changes did not occur in attached cells treated with HDACi, but their growth was suppressed as seen with annexin A1 transfected MCF7 cells. These observations suggest that apoptosis of MCF7 cells treated with HDACi is attributed to oxidative stress induced by HDACi rather than to annexin A1 induction by HDACi.Gra...