Cytostatic Effects of Dolastatin 10 and Dolastatin 15 on Human Leukemia Cell Lines

Abstract

We studied in vitro the cytostatic/cytotoxic effects of the peptides dolastatin 10 and dolastatin 15 on various human leukemia cell lines, peripheral blood mononuclear cells (PBMNC), and tonsillar mononuclear cells (tonsillar MNC). On leukemia cell lines both drugs proved to be highly potent cvtostatic agents; however, the cells were not killed even at concentrations of maximum growth-inhibition. Growth-suppression was not paralleled by induced differentiation as exposure to dolastatins did not significantly alter the immunophenotype, cytochemistry or morphology of HL-60 cells. Growth-inhibitory effects of dolastatins were reversed following the removal of the agents from the culture medium. The dolastatins inhibited proliferation of leukemia cell lines at lower concentrations than those which inhibited the growth of stimulated tonsillar MNC. The growth-inhibiting properties of the dolastatins regarding leukemia cell lines and their low toxicity towards normal MNC indicate that these agents might be promising new drugs for future experiments examining their effects on primary leukemic cells.

Key Words:

• Dolastatin
• Leukemia
• Cell lines
• Cytostatic