Blood, Vol. 93 No. 11 (June 1), 1999:
pp. 3994-4005
Alteration of Actin Organization by Jaspamide Inhibits Ruffling, but
not Phagocytosis or Oxidative Burst, in HL-60 Cells and Human Monocytes
Ina Fabian,
Drora Halperin,
Smadar Lefter,
Leonid Mittelman,
Rom
T. Altstock,
Osnat Seaon, and
Ilan Tsarfaty
From the Departments of Cell Biology and Histology, Physiology, and
Human Microbiology, Sackler School of Medicine, Tel Aviv University,
Tel Aviv, Israel.
Jaspamide, a naturally occurring cyclic peptide isolated from the
marine sponge Hemiastrella minor, has fungicidal and
growth-inhibiting activities. Exposure of promyelocytic HL-60 cells and
human monocytes to jaspamide induces a dramatic reorganization of actin
from a typical fibrous network to focal aggregates. HL-60 cells exposed to 5 × 10
8 mol/L or 107 mol/L jaspamide
exhibited a reduced proliferation rate. In addition, 107
mol/L jaspamide induced maturation of HL-60 cells as indicated by the
appearance of a lobulated nucleus in 55% ± 5% of the cells and
immunophenotypic maturation of the leukemia cells (upregulation of CD16
and CD14 B antigens). Further characterization has shown that F-actin
is aggregated both in HL-60 cells and in human monocytes exposed to
107 mol/L jaspamide. Well-spread cultured human
monocytes contracted and adopted round shapes after treatment with
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 intracellular movement in HL-60 cells and monocytes, but does not
affect phagocytic activity or respiratory burst activity. The
consequential effects of jaspamide-induced actin reorganization on
ruffling, versus its negligible effect on phagocytosis and oxidative
burst, may shed light on molecular mechanisms of actin involvement in
these processes. Jaspamide disrupts the actin cytoskeleton of normal and malignant mammalian cells with no significant effect on phagocytic activity and may, therefore, be considered as a novel therapeutic agent.
