Bortezomib sensitizes human renal cell carcinomas to TRAIL apoptosis through increased activation of caspase-8 in the death-inducing signaling complex.

ABSTRACT: Bortezomib (VELCADE) could sensitize certain human renal cell carcinoma (RCC) lines to the apoptotic effects of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Analysis of seven human RCC showed a clear increase in the sensitivity of four of the RCC to TRAIL cytotoxicity following bortezomib (5-20 nmol/L) treatment, whereas the remaining three remained resistant. Tumor cell death following sensitization had all the features of apoptosis. The enhanced antitumor activity of the bortezomib and TRAIL combination was confirmed in long-term (6 days) cancer cell outgrowth assays. The extent of proteasome inhibition by bortezomib in the various RCC was equivalent. Following bortezomib treatment, neither changes in the intracellular protein levels of various Bcl-2 and IAP family me

SUBMITTER: Brooks AD 

PROVIDER: S-EPMC2873082 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature