dolastatin-10 and Leukemia

The effects of two natural peptides, dolastatin 10 and dolastatin 15, on growth and differentiation of hematopoietic cells were studied using freshly explanted leukemia cells and continuous leukemia cell lines. The proliferation of several myeloid cell lines and of growth-factor-stimulated peripheral blood cells from patients with acute myeloid leukemia (AML) was efficiently inhibited by the two agents at concentrations between 1 and 0.01 nM. Growth inhibition was dose-dependent and reversible. Neither of the dolastatins exhibited significant cytotoxicity on dividing cells, nor did they interfere with the viability of resting cells. The 12-O-tetradecanoylphorbol 13-acetate or bryostatin I induced differentiation of AML cells was not affected by the dolastatins. Short-term exposure to the phorbol ester conferred reduced sensitivity of the cell line HL-60 to the antiproliferative effect of the drugs. Our data suggest that the dolastatins alone or in combination with other drugs could exert a role in the treatment of human myeloid leukemia.

Topics: Antineoplastic Agents; Bryostatins; Cell Differentiation; Cell Division; Depsipeptides; Humans; In Vitro Techniques; Lactones; Leukemia; Macrolides; Oligopeptides; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured