Photo-activation of the delocalized lipophilic cation D112 potentiates cancer selective ROS production and apoptosis.

ABSTRACT: Delocalized lipophilic cations (DLCs) selectively accumulate in cancer cell mitochondria and have long been explored for therapeutic applications. Although targeted effects to cancer cells are demonstrated in vitro, non-specific toxicities in vivo have hampered clinical development. Identifying the molecular mechanisms of action and enhancing selectivity are thus necessary next steps to improve these compounds and evaluate their suitability for further drug development. D112 is one such DLC with promising properties. We previously demonstrated that D112 selectively induced intrinsic apoptosis in transformed versus non-transformed cell lines. Here we show that D112 preferentially entered transformed cells where it interacted with, and damaged mitochondrial DNA, inhibited Complex I respirati

SUBMITTER: Yang N 

PROVIDER: S-EPMC5386467 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature