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

Sanguine Byun, Seung Ho Shin, Eunjung Lee, Jihoon Lee, Sung Young Lee, Lee Farrand, Sung Keun Jung, Yong Yeon Cho, Soo Jong Um, Hong Sig Sin, Youn Ja Kwon, Chengjuan Zhang, K. Tsang Benjamin, M. Bode Ann, Hyong Joo Lee, Ki Won Lee, Zigang Dong

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

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 at the same concentration. Analysis of the tumors demonstrated that ABPN treatment suppressed ErbB3 and Met and induced Nrdp1 in vivo. The data suggest that ABPN may be more suitable in combination chemotherapy with gemcitabine than the more widely used EGFR inhibitor, erlotinib.

Original languageEnglish
Pages (from-to)1580-1589
Number of pages10
JournalCarcinogenesis
Volume36
Issue number12
DOIs
Publication statusPublished - 2015 Dec 1

All Science Journal Classification (ASJC) codes

  • Cancer Research

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