Celastrol targets proteostasis and acts synergistically with a heat-shock protein 90 inhibitor to kill human glioblastoma cells.

ABSTRACT: Glioblastoma multiforme is a devastating disease of the central nervous system and, at present, no effective therapeutic interventions have been identified. Celastrol, a natural occurring triterpene, exhibits potent anti-tumor activity against gliomas in xenograft mouse models. In this study, we describe the cell death mechanism employed by celastrol and identify secondary targets for effective combination therapy against glioblastoma cell survival. In contrast to the previously proposed reactive oxygen species (ROS)-dependent mechanism, cell death in human glioblastoma cells is shown here to be mediated by alternate signal transduction pathways involving, but not fully dependent on, poly(ADP-ribose) polymerase-1 and caspase-3. Our studies indicate that celastrol promotes proteotoxic stres

SUBMITTER: Boridy S 

PROVIDER: S-EPMC4047902 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature