NF-κB activation as a pro-survival signal from pharmacological inhibition of pyruvate dehydrogenase kinase 1 in non-small-cell lung carcinoma cell models.

ABSTRACT: Targeting Pyruvate dehydrogenase kinase (PDK) has emerged as one of the potential therapeutic strategies for non-small cell lung carcinoma (NSCLC). 64, a recently reported PDK1 inhibitor derived from 2,2-dichloroacetophenone (DAP), exhibited promising anticancer effects in NSCLC models. Herein, we sought to investigate the mechanism of action of 64 in two NSCLC cell lines, namely, NCI-H1975 and NCI-H1650. We found that 64 induced intrinsic cancer cell apoptosis by releasing cytochrome C (CytC) from mitochondria, leading to caspase-3 and poly (ADP-ribose) polymerase (PARP) cleavage, which was mediated by reactive oxygen species (ROS). Moreover, we have shown that 64 induced mitochondrial membrane potential (MMP) depolarization and AMPK/MAPK activations were also ROS driven. With the aid of

SUBMITTER: Liu Q 

PROVIDER: S-EPMC12859809 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature