Enzyme-mediated depletion of l-cyst(e)ine synergizes with thioredoxin reductase inhibition for suppression of pancreatic tumor growth.

ABSTRACT: Perturbing redox homeostasis potentially constitutes a selective cancer-killing strategy. An engineered human enzyme, cyst(e)inase that degrades extracellular cysteine (l-Cys) and cystine (CSSC) leading to depletion of intracellular l-Cys and glutathione (GSH) was evaluated for its effects on pancreatic cancer cell lines. Cyst(e)inase caused oxidative stress and apoptosis in only Panc1 cells, whereas MIA-PaCa2 and BxPC3 cells demonstrated survival under conditions of cyst(e)inase-mediated l-Cys depletion through maintenance of mitochondrial metabolism and lower levels of reactive oxygen species (ROS). A correlation was also observed between thioredoxin 1 protein levels and resistance to cyst(e)inase treatment. Notably, cyst(e)inase in combination with auranofin, a thioredoxin reductase inh

SUBMITTER: Kshattry S 

PROVIDER: S-EPMC6546752 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature