QW-1624F2-2, a synthetic analogue of 1,25-dihydroxyvitamin D3, enhances the response to other deltanoids and suppresses the invasiveness of human metastatic breast tumor cells

Sujatha Sundaram, Matthew J. Beckman, Amandeep Bajwa, Jeffrey Wei, Kathleen M. Smith, Gary H. Posner, David A. Gewirtz

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The enzyme 24-hydroxylase, also known as CYP24, metabolizes 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and is an established marker of vitamin D activity. Our studies evaluated the influence of a low-calcemic 1,25(OH)2D3 analogue, QW-1624F2-2 (QW), on the regulation of CYP24 expression in MKL-4 cells, a metastatic mammary tumor cell model. 1,25(OH)2D3 and its analogue, EB 1089, stimulated CYP24 induction at both protein and transcript levels. In contrast, QW failed to produce a sustained stimulation of CYP24, due, in large part, to a reduction in the stability of the CYP24 message. QW enhanced the capacity of 1,25(OH)2D3 and EB 1089 to inhibit tumor cell proliferation by ∼2-fold. QW also blocked the sustained induction of CYP24 expression by 1,25(OH)2D3 and EB 1089, increased the potency of 1,25(OH)2D3 and EB 1089, and inhibited breast tumor cell proliferation and invasion.

Original languageEnglish (US)
Pages (from-to)2806-2814
Number of pages9
JournalMolecular Cancer Therapeutics
Volume5
Issue number11
DOIs
StatePublished - Nov 1 2006
Externally publishedYes

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Calcitriol
Breast Neoplasms
Cell Proliferation
Mixed Function Oxygenases
Vitamin D
seocalcitol
QW 1624F2-1
Enzymes
Neoplasms
Proteins

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

QW-1624F2-2, a synthetic analogue of 1,25-dihydroxyvitamin D3, enhances the response to other deltanoids and suppresses the invasiveness of human metastatic breast tumor cells. / Sundaram, Sujatha; Beckman, Matthew J.; Bajwa, Amandeep; Wei, Jeffrey; Smith, Kathleen M.; Posner, Gary H.; Gewirtz, David A.

In: Molecular Cancer Therapeutics, Vol. 5, No. 11, 01.11.2006, p. 2806-2814.

Research output: Contribution to journalArticle

Sundaram, Sujatha ; Beckman, Matthew J. ; Bajwa, Amandeep ; Wei, Jeffrey ; Smith, Kathleen M. ; Posner, Gary H. ; Gewirtz, David A. / QW-1624F2-2, a synthetic analogue of 1,25-dihydroxyvitamin D3, enhances the response to other deltanoids and suppresses the invasiveness of human metastatic breast tumor cells. In: Molecular Cancer Therapeutics. 2006 ; Vol. 5, No. 11. pp. 2806-2814.
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