The novel dithiocarbamate, DpdtC suppresses HER2-overexpressed cancer cells by up-regulating NDRG1 via inactivation of HER2-ERK 1/2 signaling.

ABSTRACT: Dithiocarbamate has been tested for its effective anti-tumor activity, but the underlying mechanism remains unclear. We previously prepared a novel diththiocarbamate derivative, DpdtC with an ability of catalase inhibition. Here, we for the first time investigated the growth inhibition effects of DpdtC on HER2-amplified cancer cells and elucidated its mechanism of action. Results showed that DpdtC exerted the potent anti-tumor effects against HER2-overexpressed SK-OV-3 and SK-BR-3 cells, especially on SK-OV-3 cells with a higher NDRG1 level, which was also confirmed in the SK-OV-3 xenograft model. Interestingly, we observed that NDRG1 was up-regulated, while membrane expression of HER2 was regressed in SK-OV-3 cells upon DpdtC treatment. In agreement, silencing endogenous NDRG1 also increa

SUBMITTER: Yang Y 

PROVIDER: S-EPMC5821706 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature