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Growth inhibition of human keratinocytes by a new vitamin D3 analogue in vitro.

Abstract
SM-10193 (26,26,26,27,27,27-hexafluoro-1 alpha,23(S),25-trihydroxyvitamin D3; F6-1,23(S),25-(OH)3D3) is one of the active vitamin D3 analogues, which is under exploration as a new therapeutic agent for psoriasis. In this paper, we present that SM-10193 induces the growth inhibition and differentiation of cultured normal human keratinocytes more effectively than 1,25(OH)2D3. The growth of keratinocytes was inhibited in the presence of 10(-11), 10(-10), 10(-9), 10(-8), 10(-7) and 10(-6) M of SM-10193 by 36.8, 42.1, 48.5, 47.6, 66.0 and 85.9% respectively. SM-10193 increased the number of involucrin positive cells (the marker for keratinocyte differentiation) from 4.9 +/- 0.1 to 12.5 +/- 0.8, 20.1 +/- 1.6 and 42.8 +/- 1.0% (P < 0.01) at 10(-8), 10(-7) and 10(-6) M, respectively. To elucidate the mechanism of SM-10193-induced growth inhibition, we analyzed cell cycle related distribution and the alteration of hyperphosphorylated and hypophosphorylated state of retinoblastoma protein (pRB). SM-10193 induces growth arrest in G1/G0 and G2 + M phases and an increase of the hypophosphorylated form of pRB more remarkably than 1,25(OH)2D3 does.
AuthorsT Kobayashi, K Hashimoto, K Yoshikawa
JournalJournal of dermatological science (J Dermatol Sci) Vol. 16 Issue 2 Pg. 158-64 (Jan 1998) ISSN: 0923-1811 [Print] Netherlands
PMID9459129 (Publication Type: Journal Article)
Chemical References
  • Retinoblastoma Protein
  • 26,26,26,27,27,27-hexafluoro-1,23,25-trihydroxyvitamin D3
  • Cholecalciferol
  • Calcitriol
Topics
  • Calcitriol (analogs & derivatives, pharmacology, therapeutic use)
  • Cell Cycle (drug effects)
  • Cell Differentiation (drug effects)
  • Cell Division (drug effects)
  • Cholecalciferol (analogs & derivatives, pharmacology, therapeutic use)
  • Dose-Response Relationship, Drug
  • Humans
  • Keratinocytes (cytology, drug effects)
  • Psoriasis (drug therapy)
  • Retinoblastoma Protein (drug effects, metabolism)

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