Therapeutic Potential of a Novel Smac/DIABLO in Breast Cancer

Abstract : The objectives of this study was to examine the intracellular mechanisms by which Smac/DIABLO sensitizes TRAiL-resistant breast cancer cells to undergo apoptosis, and enhances the therapeutic potential of tamoxifen, doxorubicin and paclitaxel. Overexpression of Smac/DIABLO gene or Smac peptide enhances the apoptosis-inducing potential of tamoxifen, doxorubicin and paclitaxel, and sentitizes TRAiL-resistant breast cancer cell lines. The effects of combination treatments with Smac/DIABLO and drugs on apoptosis, growth inhibition, and caspase activation were higher than the single treatment alone. Thus, the combination of Smac/DIABLO with tamoxifen, doxorubicin, paclitaxel or TRAIL may be used as a new therapeutic approach for breast cancer therapy.