Biological activities of geometrical isomers of retinoic acid on human acute promyelocytic leukemia cell line HL-60 were analized by strictly excluding the effects of artificial isomerization. Varying from previous reports, 9-
cis-retinoic acid showed over tenfold higher activity than all-
trans-retinoic acid. Activity of 13-
cis-retinoic acid corresponded roughly to that of all-
trans-retinoic acid, and activity of 9, 13-di-
cis-retinoic acid was approximately 1/10 of the level of all-
trans-retinoic acid. Activities of the isomers on HL-60 cells to inhibit growth and to induce differentiation into granulocytes were parallel. all-
trans-Retinoic acid and 9-
cis-retinoic acid acted synergetically on HL-60 cells. Further, all-
trans-retinoic acid acted additively with 13-
cis-retinoic acid and with 9, 13-di-
cis-retinoic acid. In contrast, 9-
cis-retinoic acid acted synergetically with 13-
cis-retinoic acid and with 9, 13-di-
cis-retinoic acid.
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