Alteration of actin organization by jaspamide inhibits ruffling, but not phagocytosis or oxidative burst, in HL-60 cells and human monocytes

Jaspamide, a naturally occurring cyclic peptide isolated from the marine sp onge Hemiastrella minor, has fungicidal and growth-inhibiting activities. E xposure of promyelocytic HL-60 cells and human monocytes to jaspamide induc es a dramatic reorganization of actin from a typical fibrous network to foc al aggregates. HL-60 cells exposed to 5 x 10(-8) mol/L or 10(-7) mol/L jasp amide exhibited a reduced proliferation rate. In addition, 10(-7) mol/L jas pamide induced maturation of HL-60 cells as indicated by the appearance of a lobulated nucleus in 55% +/- 5% of the cells and immunophenotypic maturat ion of the leukemia cells (upregulation of CD16 and CD14 B antigens). Furth er characterization has shown that F-actin is aggregated both in HL-60 cell s and in human monocytes exposed to 10(-7) mol/L jaspamide. Well-spread cul tured human monocytes contracted and adopted round shapes after treatment w ith jaspamide, Moreover, a dose-dependent increase in both total actin and de novo synthesized portions of the soluble actin was observed in jaspamide -treated HL-60 cells. Jaspamide treatment inhibits ruffling and intracellul ar movement in HL-60 cells and monocytes, but does not affect phagocytic ac tivity or respiratory burst activity. The consequential effects of jaspamid e-induced actin reorganization on ruffling, versus its negligible effect on phagocytosis and oxidative burst, may shed light on molecular mechanisms o f actin involvement in these processes. Jaspamide disrupts the actin cytosk eleton of normal and malignant mammalian cells with no significant effect o n phagocytic activity and may, therefore, be considered as a novel therapeu tic agent. (C) 1999 by The American Society of Hematology.