Inhibition of branched-chain alpha-keto acid dehydrogenase kinase augments the sensitivity of ovarian and breast cancer cells to paclitaxel.

ABSTRACT:

Context

Many cancer patients who initially respond to chemotherapy eventually develop chemoresistance, and to address this, we previously conducted a RNAi screen to identify genes contributing to resistance. One of the hits from the screen was branched-chain α-keto acid dehydrogenase kinase (BCKDK). BCKDK controls the metabolism of branched-chain amino acids (BCAAs) through phosphorylation and inactivation of the branched-chain α-keto acid dehydrogenase complex (BCKDH), thereby inhibiting catabolism of BCAAs.

Methods

We measured the impact on paclitaxel sensitivity of inhibiting BCKDK in ovarian and breast cancer cell lines.

Results

Inhibition of BCKDK using siRNA or two chemical inhibitors (BCKDKi) was synergistic with paclitaxel in both breast and ovarian cancer cel

SUBMITTER: Ibrahim SL 

PROVIDER: S-EPMC9977917 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature