19-nor-1α,25-dihydroxyvitamin D2 (Paricalcitol) inhibits the proliferation of human pancreatic cancer cells in vitro and in vivo

Gary G. Schwartz, Dawn Eads, Christine Naczki, Scott Northrup, Tai Chen, Constantinos Koumenis

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

1,25-dihydroxyvitamin D3, (1,25(OH)2D3; calcitriol), the hormonal form of vitamin D, exerts growth-inhibitory, pro-apoptotic and anti-metastatic effects on tumor cells in vitro and in vivo but its clinical use is limited by its calcemic effects. Previous studies have shown that the antiproliferative effects of the less calcemic calcitriol analog 19-nor-1,25-(OH)2D2 (paricalcitol) on prostate tumor cell lines are indistinguishable from those of 1,25(OH)2D3. We therefore investigated the anti-proliferative effects of paricalcitol on the growth of pancreatic tumor cell lines in vitro and in vivo. Both 1,25(OH) 2D3 and paricalcitol inhibited the growth of BxPC-3, Hs700T and AsPC-1 lines in a dose-dependent manner. This antiproliferative activity correlated with upregulation of the cell cycle inhibitors p21 (Waf1/CIP1) and p27(Kip1). A fourth pancreatic cell line, Hs766T, was unresponsive to both paricalcitol and calcitriol. Hs766T cells also failed to upregulate p21/Waf-1/Cip1 or p27/KiP in response to treatments with these agents. Paricalcitol, given three times per week, inhibited the growth of AsPC-1 pancreatic tumor cell xenografts in nude mice at a dose that did not cause hypercalcaemia. Tumor inhibition was accompanied by in vivo upregulation of p21 and p27 expression. Given the few therapeutic options for patients with pancreatic cancer, further exploration of paricalcitol, an FDA-approved medication, is warranted.

Original languageEnglish (US)
Pages (from-to)430-436
Number of pages7
JournalCancer Biology and Therapy
Volume7
Issue number3
DOIs
Publication statusPublished - Mar 2008

    Fingerprint

Keywords

  • Pancreatic cancer
  • Vitamin D
  • Zemplar
  • p21
  • p27

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

Cite this