Hexafluoro-1,25-dihydroxyvitamin D3 has markedly increased potency in inhibiting proliferation of cultured human keratinocytes compared with 1,25-dihydroxyvitamin D3.
BACKGROUND
Although topical 1,25-dihydroxyvitamin D3 (calcitriol, 1, 25(OH)2D3) and its analogues, calcipotriol and tacalcitol, are effective for patients with psoriasis, some patients show little or no response. There is a need to develop more potent analogues of 1, 25(OH)2D3. Hexafluoro-1,25(OH)2D3 (F6-1,25(OH)2D3) is at least 10 times more potent than 1,25(OH)2D3 on calcium metabolism.


OBJECTIVE
We were interested in whether F6-1,25(OH)2D3 was also more potent than 1,25(OH)2D3 in inhibiting normal human and psoriatic keratinocyte proliferation.


METHODS
The antiproliferative activity of F6-1,25(OH)2D3 and 1,25(OH)2D3 was determined by 3H-thymidine incorporation into keratinocyte DNA and by counting basal cells.


RESULTS
F6-1,25(OH)2D3 was approximately 10-fold more active and had a longer lasting antiproliferative effect than 1,25(OH)2D3 on normal human keratinocytes, and was about 100-fold more potent than 1, 25(OH)2D3 on human psoriatic keratinocytes as determined by 3H-thymidine incorporation. F6-1,25(OH)2D3 also caused a dose-dependent decrease in the number of basal cells and was 100-fold more active than 1,25(OH)2D3.


CONCLUSIONS
The increased potency and the long-lasting effects of F6-1,25(OH)2D3 suggest that F6-1,25(OH)2D3 may be a potent candidate agent for treating psoriasis.
Chen
T C
TC
Vitamin D, Skin and Bone Research Laboratory and Endocrine, Nutrition and Diabetes Section, Department of Medicine, Boston University Medical Center, 715 Albany Street, Boston, MA 02118, USA.
Holick
M F
MF
D002117:Calcitriol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007231:Infant, Newborn; D015603:Keratinocytes / Q000187:drug effects* / Q000473:pathology; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology; D005466:Fluorocarbons
D002117:Calcitriol; C040488:26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3; D005466:Fluorocarbons