The retinoic acid derivative, ABPN, inhibits pancreatic cancer through induction of Nrdp1.

ABSTRACT: Combination chemotherapy for the treatment of pancreatic cancer commonly employs gemcitabine with an EGFR inhibitor such as erlotinib. Here, we show that the retinoic acid derivative, ABPN, exhibits more potent anticancer effects than erlotinib, while exhibiting less toxicity toward noncancerous human control cells. Low micromolar concentrations of ABPN induced apoptosis in BxPC3 and HPAC pancreatic cancer cell lines, concomitant with a reduction in phosphorylated EGFR as well as decreased ErbB3, Met and BRUCE protein levels. The degradation of ErbB3 is a result of proteasomal degradation, possibly due to the ABPN-dependent upregulation of Nrdp1. Administration of ABPN showed significant reductions in tumor size when tested using a mouse xenograft model, with higher potency than erlotinib

SUBMITTER: Byun S 

PROVIDER: S-EPMC4850933 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature