Bortezomib primes glioblastoma including glioblastoma stem cells for TRAIL by increasing tBid stability and mitochondrial apoptosis

Glioblastoma is refractory to current treatment approaches calling for novel strategies. One emerging option is proteasome inhibition as some antitumor activity in glioblastoma has recently been shown. Here, we report that the proteasome inhibitor Bortezomib primes glioblastoma cells including glioblastoma stem cells to TRAIL-induced apoptosis in vitro and in vivo by increasing tBid stability and facilitating mitochondrial apoptosis. Investigations into the underlying molecular mechanisms reveal that Bortezomib and TRAIL act in concert to cause accumulation of tBid, the active cleavage product of Bid, and the st…