Biological evaluation of new vitamin D2 analogues

Research output: Contribution to journalArticle

Authors

  • Aoife Corcoran
  • Maria A. Bermudez
  • Samuel Seoane
  • Roman Perez-fernandez
  • Małgorzata Krupa
  • Anita Pietraszek
  • Michał Chodyński
  • Andrzej Kutner
  • Ewa Marcinkowska

Colleges, School and Institutes

Abstract

1,25-dihydroxyvitamin D3 (1,25D), a steroid hormone which regulates calcium/phosphate homeostasis, has a broad spectrum of anti-cancer activities, including differentiation of acute myeloid leukemia (AML) cells. In order to avoid undesirable side effects such as hypercalcemia, low-calcemic analogues should be produced for therapeutic purposes. In this paper, we describe biological activities of double-point modified analogues of vitamin D2 and we compare them to 1,25D and to paricalcitol, the drug used to treat secondary hyperparathyroidism. In vivo, our new analogues have lower calcemic effects, and lower toxicity in comparison to 1,25D. They have enhanced pro-differentiating and transcription-inducing activities in AML cells. Interestingly, differentiation effects do not correlate with the affinities of the analogues to the vitamin D receptor (VDR).

Details

Original languageEnglish
JournalThe Journal of Steroid Biochemistry and Molecular Biology
Early online date30 Sep 2015
Publication statusE-pub ahead of print - 30 Sep 2015

Keywords

  • vitamin D analogues, vitamin D receptor, leukemia, differentiation, calcemic effects, keratinocytes