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Carcinogenesis. 2015 Dec;36(12):1580-9. doi: 10.1093/carcin/bgv148. Epub 2015 Oct 13.

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

Author information

1
Department of Cellular and Molecular Biology, The Hormel Institute, University of Minnesota, Austin, MN 55912, USA, Department of Agricultural Biotechnology, Seoul National University, Advanced Institutes of Convergence Technology, Seoul National University, Seoul 151-742, Republic of Korea.
2
Department of Cellular and Molecular Biology, The Hormel Institute, University of Minnesota, Austin, MN 55912, USA, Program in Biomedical Informatics and Computational Biology, University of Minnesota, Minneapolis, MN 55454, USA.
3
Department of Agricultural Biotechnology, Seoul National University, Traditional Alcoholic Beverage Research Team, Korea Food Research Institute, Seongnam, Republic of Korea.
4
Department of Agricultural Biotechnology, Seoul National University.
5
Department of Cellular and Molecular Biology, The Hormel Institute, University of Minnesota, Austin, MN 55912, USA.
6
Department of Agricultural Biotechnology, Seoul National University, Yuhan Research Institute, Yuhan Corporation, Giheung-gu, Yongin-si 416-1, Republic of Korea.
7
Department of Bioscience and Biotechnology/Institute of Bioscience, BK21 Graduate Program, Sejong University, Seoul, Republic of Korea, CheBiGen Inc, BioPark infrastructure BI. Business, 452-79 Jang-Dong, Jeonju, Jeollabukdo, Republic of Korea.
8
CheBiGen Inc, BioPark infrastructure BI. Business, 452-79 Jang-Dong, Jeonju, Jeollabukdo, Republic of Korea.
9
Department of Cellular and Molecular Biology, The Hormel Institute, University of Minnesota, Austin, MN 55912, USA, Department of Molecular Pathology, The Affiliated Cancer Hospital, Zhengzhou University, Zhengzhou, China and.
10
Department of Agricultural Biotechnology, Seoul National University, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa Hospital Research Institute, Ottawa, Canada.
11
Department of Agricultural Biotechnology, Seoul National University, Advanced Institutes of Convergence Technology, Seoul National University, Seoul 151-742, Republic of Korea.
12
Department of Cellular and Molecular Biology, The Hormel Institute, University of Minnesota, Austin, MN 55912, USA, zgdong@hi.umn.edu.

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.

PMID:
26464195
PMCID:
PMC4850933
DOI:
10.1093/carcin/bgv148
[Indexed for MEDLINE]
Free PMC Article

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