Disruption of mitochondrial electron transport chain function potentiates the pro-apoptotic effects of MAPK inhibition.

ABSTRACT: The mitochondrial network is a major site of ATP production through the coupled integration of the electron transport chain (ETC) with oxidative phosphorylation. In melanoma arising from the V600E mutation in the kinase v-RAF murine sarcoma viral oncogene homolog B (BRAF^V600E), oncogenic signaling enhances glucose-dependent metabolism while reducing mitochondrial ATP production. Likewise, when BRAF^V600E is pharmacologically inhibited by targeted therapies (e.g. PLX-4032/vemurafenib), glucose metabolism is reduced, and cells increase mitochondrial ATP production to sustain survival. Therefore, collateral inhibition of oncogenic signaling and mitochondrial respiration may help enhance the therapeutic benefit of targeted therapies. Honokiol (HKL) is a well tolerat

SUBMITTER: Trotta AP 

PROVIDER: S-EPMC5512068 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature