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.