Cotylenin A, a plant-growth regulator, induces the differentiation in murine and human myeloid leukemia cells.
Protein factors playing a significant part in differentiation and development have been recently elucidated. However, low molecular factors which also seem to be essential remain still unknown, although only retinoic 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 the concentrations above 12.5 microg/ml (20 microM) cotylenin A induced the functional and morphological differentiation in murine (M1) and human myeloid leukemia (HL-60) cells. Although cotylenin A has some similarity to PMA both in carbotricyclic diterpene structure and in biological activity (i.e. differentiation-induction of HL-60 cells into macrophages), the activation of PKC and the elevation of Ca2+-levels by cotylenin A were not observed. Quite recently it has been reported that fusicoccin (closely related to cotylenin A)-targets are 14-3-3 proteins, which are at the crosspoint of a huge array of signalling and regulatory pathways. These results suggest that cotylenin A might become a useful tool for the elucidation of molecular mechanisms of differentiation and development.
Asahi
K
K
The Institute of Physical and Chemical Research (RIKEN), Saitama, Japan.
Honma
Y
Y
Hazeki
K
K
Sassa
T
T
Kubohara
Y
Y
Sakurai
A
A
Takahashi
N
N
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002963:Cladosporium / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D007951:Leukemia, Myeloid / Q000201:enzymology / Q000473:pathology*; D051379:Mice; D009113:Muramidase / Q000096:biosynthesis; D010937:Plant Growth Regulators / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004224:Diterpenes; D006131:Growth Inhibitors; D010937:Plant Growth Regulators; C423222:cotylenin A; D011493:Protein Kinase C; D009113:Muramidase; D002118:Calcium