COTYLENIN-A, A PLANT-GROWTH REGULATOR, INDUCES THE DIFFERENTIATION INMURINE AND HUMAN MYELOID-LEUKEMIA CELLS

Protein factors playing a significant part in differentiation and deve lopment have been recently elucidated. However, low molecular factors which also seem to be essential remain still unknown, although only re tinoic acid has become such a candidate. Cotylenins had been isolated as the plant-growth regulators, and have been found to affect a number of physiological processes of higher plants. Here we report that at t he concentrations above 12.5 mu g/ml (20 mu M) cotylenin A induced the functional and morphological differentiation in murine (M1) and human myeloid leukemia (HL-60) cells, Although cotylenin A has some similar ity to PMA both in carbotricyclic diterpene structure and in biologica l activity (i.e. differentiation-induction of HL-60 cells into macroph ages), the activation of PRC and the elevation of Ca2+-levels by cotyl enin A were not observed. Quite recently it has been reported that fus icoccin (closely related to cotylenin A)-targets are 14-3-3 proteins, which are at the crosspoint of a huge array of signalling and regulato ry pathways. These results suggest that cotylenin A might become a use ful tool for the elucidation of molecular mechanisms of differentiatio n and development. (C) 1997 Academic Press.