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.

Abstract

The enzyme 24-hydroxylase, also known as CYP24, metabolizes 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] and is an established marker of vitamin D activity. Our studies evaluated the influence of a low-calcemic 1,25(OH)(2)D(3) analogue, QW-1624F2-2 (QW), on the regulation of CYP24 expression in MKL-4 cells, a metastatic mammary tumor cell model. 1,25(OH)(2)D(3) 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)(2)D(3) and EB 1089 to inhibit tumor cell proliferation by approximately 2-fold. QW also blocked the sustained induction of CYP24 expression by 1,25(OH)(2)D(3) and EB 1089, increased the potency of 1,25(OH)(2)D(3) and EB 1089, and inhibited breast tumor cell proliferation and invasion.

• Authors: Sujatha Sundaram, Matthew J Beckman, Amandeep Bajwa, Jeffrey Wei, Kathleen M Smith, Gary H Posner, David A Gewirtz
• Journal: Molecular cancer therapeutics (Mol Cancer Ther) Vol. 5 Issue 11 Pg. 2806-14 (Nov 2006) ISSN: 1535-7163 [Print] United States
• PMID: 17121927 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antineoplastic Agents
• QW 1624F2-1
• Receptors, Calcitriol
• Steroid Hydroxylases
• Vitamin D3 24-Hydroxylase
• Calcitriol

Topics

• Antineoplastic Agents (pharmacology, therapeutic use)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Calcitriol (analogs & derivatives, pharmacology, therapeutic use)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Female
• Humans
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Promoter Regions, Genetic (drug effects)
• Receptors, Calcitriol (metabolism)
• Steroid Hydroxylases (genetics, metabolism)
• Vitamin D3 24-Hydroxylase