22-27Acitretin, a beneficial retinoid, was
shown to undergo constant structural interconversions among its geometrical
isomers (all-trans-acitretin, 9-cis-acitretin, 13-cis-acitretin,
9, 13-di-cis-acitretin, etc.) by photoisomerization under natural light.
The photoisomerization was zero order reaction with an apparent velocity of
4×10-7 M/min under illumination by
white fluorescent lamps (1, 200 1x). An equilibrium
mixture of the geometrical isomers (all-trans-acitretin 20%, 9-cis-acitretin
15%, 13-cis-acitretin 30%, 9, 13-di-cis-acitretin 15%, and unidentified
compounds 20%) was formed at around 30 min. Equilibrium mixtures with similar
composition were obtained by photoisomerization reactions starting from other
geometrical isomers. Geometrical isomers of
acitretin thus formed, showed different effects to induce differentiation of human
acute promyelocytic leukemia cells (HL-60 cells): activity of all-trans-acitretin
(ED50, 3.2×10-6M), 9-cis-acitretin (ED50,
2.3×10-5M), 13-cis-acitretin (ED50, 1.1×10-5M),
9, 13-di-cis-acitretin (ED50, 2.6×10-6M)
9-cis-Acitretin acted synergistically with all-trans-acitretin, 13-cis-acitretin
and 9, 13-di-cis-acitretin on HL-60 cells. On the other side, all-trans-acitretin,
13-cis-acitretin and 9, 13-di-cis-acitretin acted additively. Geometrical
isomers of acitretin showed different effects on differentiation of human epidermal
keratinocytes; expression of keratinocyte differentiation markers, keratin 1 and
kerati 10, were suppressed more strongly by 9-cis-acitretin and 13-cis-acitretin
as compared to all-trans-acitretin or 9, 13-di-cis-acitretin