Superior efficacy of the antifungal agent ciclopirox olamine over gemcitabine in pancreatic cancer models.

ABSTRACT: Ciclopirox olamine (CPX) is an antifungal agent that has recently demonstrated promising anti-neoplastic activity against hematologic and solid tumors. Here, we evaluated CPX compared with gemcitabine alone as well as their combination in human pancreatic cancer cell lines; BxPC-3, Panc-1, and MIA PaCa-2 and in humanized xenograft mouse models. We also examined the preclinical pharmacodynamic activity of CPX. CPX caused a pronounced decrease in cell proliferation and clonogenic growth potential. These inhibitory effects were accompanied by induction of reactive oxygen species (ROS), which were strongly associated with reduced Bcl-xL and survivin levels and activation of a panel of caspases, especially caspase-3, and finally resulted in apoptotic death. CPX-induced apoptosis was associated

SUBMITTER: Mihailidou C 

PROVIDER: S-EPMC5828195 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature