Discovery of Mitochondrial Transcription Inhibitors Active in Pancreatic Cancer Cells.

ABSTRACT: Mitochondrial dysfunction is a hallmark of cancer cells and targeting cancer mitochondria has emerged as a promising anti-cancer therapy. Previously, we repurposed chlorambucil by conjugating it to a mitochondrial targeting triphenylphosphonium (TPP) group to design Mito-Chlor, a novel agent that acts on mitochondria DNA (mtDNA). Herein, we show that Mito-Chlor, but not chlorambucil, inhibits the nascent transcription of mtDNA. Clustering analysis of transcriptomic profile of our Bru-seq database led to the identification of another mitochondrial transcription inhibitor SQD1, which inhibits the proliferation of MIA PaCa-2 cells with an IC₅₀ of 1.3 μM. Interestingly, Mito-Chlor reduces expression of mitochondrial proteins, interferes with mitochondria membrane potential, and impa

SUBMITTER: Chen W 

PROVIDER: S-EPMC7719573 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature