Bortezomib antagonizes microtubule-interfering drug-induced apoptosis by inhibiting G2/M transition and MCL-1 degradation.

ABSTRACT: Inhibition of the proteasome is considered as a promising strategy to sensitize cancer cells to apoptosis. Recently, we demonstrated that the proteasome inhibitor Bortezomib primes neuroblastoma cells to TRAIL-induced apoptosis. In the present study, we investigated whether Bortezomib increases chemosensitivity of neuroblastoma cells. Unexpectedly, we discover an antagonistic interaction of Bortezomib and microtubule-interfering drugs. Bortezomib significantly attenuates the loss of cell viability and induction of apoptosis on treatment with Taxol and different vinca alkaloids but not with other chemotherapeutics, that is, Doxorubicin and Cisplatinum. Importantly, Bortezomib inhibits G2/M transition by inhibiting proteasomal degradation of cell cycle regulatory proteins such as p21, thereb

SUBMITTER: Rapino F 

PROVIDER: S-EPMC3847318 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature