Targeting Oxidative Stress With Auranofin or Prima-1^Met to Circumvent p53 or Bax/Bak Deficiency in Myeloma Cells.

ABSTRACT: Prima-1^Met (APR-246) was previously shown to be dependent on glutathione inhibition and on ROS induction in cancer cells with mutated or deleted TP53. Because this ROS induction was, at least in part, due to a direct interference with the thioredoxin reductase enzyme, we investigated whether activity of Prima-1^Met could be mimicked by auranofin, an inhibitor of the thioredoxin reductase. We thus compared the activity of auranofin and Prima-1^Met in 18 myeloma cell lines and in 10 samples from patients with multiple myeloma or plasma cell leukemia. We showed that, similar to Prima-1^Met, the activity of auranofin was not dependent on either TP53 status or p53 expression; was inhibited by N-acetyl-L-cysteine, a ROS scavenger; displayed

SUBMITTER: Tessoulin B 

PROVIDER: S-EPMC6414792 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature