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 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 x 10(-8) mol/L or 10(-7) mol/L jaspamide exhibited a reduced proliferation rate. In addition, 10(-7) 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 10(-7) 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.
Fabian
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Departments of Cell Biology and Histology, Physiology, and Human Microbiology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Halperin
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Lefter
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Mittelman
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Altstock
R T
RT
Seaon
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O
Tsarfaty
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I
D000199:Actins / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D000970:Antineoplastic Agents / Q000494:pharmacology*; D047630:Depsipeptides; D019281:Dimerization; D018922:HL-60 Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D006801:Humans; D008854:Microscopy, Electron; D009000:Monocytes / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects*; D016897:Respiratory Burst / Q000187:drug effects*
D000199:Actins; D000970:Antineoplastic Agents; D047630:Depsipeptides; D010456:Peptides, Cyclic; C057531:jasplakinolide