Biological activity of (all-E)-beta-apo-12'-carotenoic acid and the geometrical isomers on human acute promyelocytic leukemia cell line HL-60.
(all-E)-beta-Apo- 12'-carotenoic acid and a series of the geometrical isomers were synthesized and their biological activities to inhibit growth and to induce differentiation of human acute promyelocytic leukemia cell line HL-60 were analyzed. It was found that (all-E)-beta-apo- 12'-carotenoic acid (I, Fig. 1) and (15' -Z)-apo- 12'-carotenoic acid (II, Fig. 1) showed strong activity both in inhibition of growth and the induction of differentiation. The biological activity of (13'-Z)-beta-apo- 12'-carotenoic acid (III, Fig. 1) was modest, while that of (13', 15'-di-Z)-beta-apo- 12'-carotenoic acid (IV, Fig. 1) was negligible. (all-E)-beta-Apo- 12'-carotenoic acid and the geometrical isomers acted additively with (all-E)-retinoic acid, and synergetically with (9-Z)-retinoic acid. In accord with our previous report, biological activities of (all-E)-beta-apo- 14'-carotenoic acid (V, Fig. 1) and of (15-Z)-beta-apo- 14'-carotenoic acid (VI, Fig. 1) were very weak. It was indicated that (all-E)-beta-apo- 12'-carotenoic acid, an intermediate metabolite of excentric cleavage pathway of beta-carotene, per se may exert the biological function.
Suzuki
T
T
Department of Clinical Genetics (II), Tokyo Metropolitan Institute of Medical Science, Japan.
Matsui
M
M
Murayama
A
A
D002338:Carotenoids / Q000737:chemistry / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D015394:Molecular Structure; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D019207:beta Carotene / Q000378:metabolism
C101577:apo-12'-carotenoic acid; D019207:beta Carotene; D002338:Carotenoids; D014212:Tretinoin