Thapa B et al. - TRAIL induces apoptosis in variety of cancer cells without affecting most normal cells. Thus, TRAIL is a promising agent for cancer therapy. In the current study, the combination of siRNA targeting BCL2L12 and TRAIL was shown to be a highly effective synergistic pair in breast cancer cells with a minimal effect on non-transformed cells.

Methods

• Protein targets silencing sensitized breast cancer cells against TRAIL were screened with an siRNA library against 446 human apoptosis-related proteins in MDA-231 cells.

Results

• Using a cationic lipopolymer (PEI-alpha-LA) for delivery of library members, 16 siRNAs were identified that sensitized the TRAIL-induced death in MDA-231 cells.
• Silencing BCL2L12 and SOD1 targets sensitized TRAIL-mediated cell death in MDA-231 cells as well as TRAIL resistant breast cancer cells (MCF-7).
• The combination of TRAIL and siRNA silencing BCL2L12 had no effect in normal human umbilical vein cells and human bone marrow stromal cell. The silencing of BCL2L12 and SOD1 enhanced TRAIL-mediated apoptosis in MDA-231 cells via synergistically activating capsase-3 activity.
• siRNAs targeting BCL2L12 and SOD1 as a novel regulator of TRAIL-induced cell death in breast cancer cells.