Hexafluoro-1,25-dihydroxyvitamin D3 has markedly increased potency in inhibiting proliferation of cultured human keratinocytes compared with 1,25-dihydroxyvitamin D3

✍ Scribed by T.C. Chen; M.F. Holick

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 409 KB
• Volume: 143
• Category: Article
• ISSN: 0007-0963
• DOI: 10.1046/j.1365-2133.2000.03593.x

✦ Synopsis

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.

Objectives:

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.