Differentiation of human acute myeloid leukaemia cells in primary culture in response to cotylenin A, a plant growth regulator.

Cotylenin A, which has a diterpenoid tricarbocyclic skeleton, has been isolated as a plant growth regulator, has been shown to affect several physiological processes of higher plants and have differentiation-inducing activity in several myeloid leukaemia cell lines. We examined the effect of cotylenin A on the differentiation of leukaemic cells that were freshly isolated from acute myeloid leukaemia (AML) patients in primary culture. Cotylenin A significantly stimulated both functional and morphological differentiation of leukaemia cells in 9 out of 12 cases. This differentiation-inducing activity was more potent than those of all-trans retinoic acid and 1alpha,25-dihydroxyvitamin D3 (VD3). Treatment with a combination of cotylenin A and VD3 was more effective than cotylenin A or VD3 alone at inducing the monocytic differentiation of AML cells.

Induction of the monocytic differentiation of myeloid leukaemia cells by cotylenin A, a plant growth regulator.

Regulators that play an important role in the differentiation and development of plants or invertebrates may also affect the differentiation of human leukaemia cells through a common signal transduction system, and might be clinically useful for treating acute myeloid leukaemia. Cotylenin A has been isolated as a plant growth regulator. We examined the effects of cotylenin A on the differentiation of several myelogenous leukaemia cells, and found that cotylenin A is a potent and novel inducer of the monocytic differentiation of human myeloid leukaemia cells. Cotylenin A induced the functional and morphological differentiation of myeloblastic and promyelocytic leukaemia cells, but did not effectively induce the differentiation of monocytoid leukaemia cells. Cotylenin A-induced differentiation was not affected by several inhibitors of signal transduction, suggesting that this inducer exhibits a unique mode of action.

A vegetalizing inducing factor. Isolation and chemical properties.

A vegetalizing factor which induces the formation of endodermal and mesodermal organs in amphibian gastrula ectoderm was purified from chicken embryos. Preparative sodium dodecyl sulfate polyacrylamide electrophoresis and gel permeation chromatography on sephadex with different eluants were employed. In buffer containing 6 M urea the molecular weight of the factor was estimated to about 28 000-30 000. In buffer containing sodium dodecyl sulfate (SDS) the factor partially dissociates to smaller polypeptide chains. Because an equilibrium between molecules of different size is established, SDS-containing buffers are not suitable for preparative purposes. In 50%-70% formic acid the factor completely dissociates into smaller peptide chains (Mr about 13 000-15 000). Furthermore, very little absorption of the factor to the gel matrices or glass surfaces is observed in formic acid. The final purification can be achieved by high-performance gel permeation chromatography with glycerolpropyl-treated silica gel as column packing and 50% formic acid as eluant.