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.
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.
Sundaram
Sujatha
S
Department of Surgery, Dartmouth Medical School, One Medical Center Drive, HB 7850, Lebanon, NH 03756, USA. Sujatha.Sundaram@dartmouth.edu
Beckman
Matthew J
MJ
Bajwa
Amandeep
A
Wei
Jeffrey
J
Smith
Kathleen M
KM
Posner
Gary H
GH
Gewirtz
David A
DA
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011401:Promoter Regions, Genetic / Q000187:drug effects; D018167:Receptors, Calcitriol / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase
D000970:Antineoplastic Agents; C113641:QW 1624F2-1; D018167:Receptors, Calcitriol; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol