The thiosemicarbazone Me₂NNMe₂ induces paraptosis by disrupting the ER thiol redox homeostasis based on protein disulfide isomerase inhibition.

ABSTRACT: Due to their high biological activity, thiosemicarbazones have been developed for treatment of diverse diseases, including cancer, resulting in multiple clinical trials especially of the lead compound Triapine. During the last years, a novel subclass of anticancer thiosemicarbazones has attracted substantial interest based on their enhanced cytotoxic activity. Increasing evidence suggests that the double-dimethylated Triapine derivative Me₂NNMe₂ differs from Triapine not only in its efficacy but also in its mode of action. Here we show that Me₂NNMe₂- (but not Triapine)-treated cancer cells exhibit all hallmarks of paraptotic cell death including, besides the appearance of endoplasmic reticulum (ER)-derived vesicles, also mitochondrial swelling an

SUBMITTER: Hager S 

PROVIDER: S-EPMC6189190 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature