Antiproliferative effects and mechanisms of liver X receptor ligands in pancreatic ductal adenocarcinoma cells

Nicholes R. Candelaria, Sridevi Addanki, Jine Zheng, Trang Nguyen-Vu, Husna Karaboga, Prasenjit Dey, Chiara Gabbi, Lise Lotte Vedin, Ka Liu, Wanfu Wu, Philip K. Jonsson, Jean Z. Lin, Fei Su, Lakshmi Reddy Bollu, Sally E. Hodges, Amy L. McElhany, Mehdi A. Issazadeh, William E. Fisher, Michael M. Ittmann, Knut R. SteffensenJan-Ake Gustafsson, Chin Yo Lin

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is difficult to detect early and is often resistant to standard chemotherapeutic options, contributing to extremely poor disease outcomes. Members of the nuclear receptor superfamily carry out essential biological functions such as hormone signaling and are successfully targeted in the treatment of endocrine-related malignancies. Liver X receptors (LXRs) are nuclear receptors that regulate cholesterol homeostasis, lipid metabolism, and inflammation, and LXR agonists have been developed to regulate LXR function in these processes. Intriguingly, these compounds also exhibit antiproliferative activity in diverse types of cancer cells. In this study, LXR agonist treatments disrupted proliferation, cell-cycle progression, and colony-formation of PDAC cells. At the molecular level, treatments downregulated expression of proteins involved in cell cycle progression and growth factor signaling. Microarray experiments further revealed changes in expression profiles of multiple gene networks involved in biological processes and pathways essential for cell growth and proliferation following LXR activation. These results establish the antiproliferative effects of LXR agonists and potential mechanisms of action in PDAC cells and provide evidence for their potential application in the prevention and treatment of PDAC.

Original languageEnglish (US)
Article numbere106289
JournalPLoS ONE
Volume9
Issue number9
DOIs
StatePublished - Sep 3 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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