Description
Cytochalasin D (22144-77-0) is a potent inhibitor of actin polymerization which also causes the disruption of actin filaments. More potent that cytochalasin B (10-fold) and does not inhibit monosaccharide transport across cell membranes. Disruption of actin microfilaments leads to activation of p53. Cell permeable
Chemical Properties
Powder
Uses
A cell cycle arresting compound used in actin polymerization studies and cytological research
Uses
Cytochalasin D is the most studied of the cytochalasins. Like most of the members of this mycotoxin class, cytochalasin D exhibits potent inhibition of actin filament function leading to cell death by apoptosis. This led to early investigation of the metabolite as an antitumour agent. Cytochalasin D has become one of the standard cellular probes for investigating the role of actin in cell biology.
Uses
Cytochalasin D acts as an anti-hypertensive drug acting on human intestinal epithelial caco-2 cells. Also has activity in HMG-CoA reductase inhibitors used in the lowering of cholesterol. Actin inhib
itor, actin polymerization inhibitor affecting cell movement, growth, phagocytosis and even secretion.
Definition
ChEBI: An organic heterotricyclic compound that is a mycotoxin produced by Helminthosporium and other moulds which is cell permeable and a potent inhibitor of actin polymerisation and DNA synthesis.
General Description
Needles or fluffy white powder.
Reactivity Profile
CYTOCHALASIN D may be sensitive to exposure to heat. CYTOCHALASIN D can react with strong oxidizing agents, strong acids and strong bases. .
Fire Hazard
Flash point data for CYTOCHALASIN D are not available; however, CYTOCHALASIN D is probably combustible.
Biological Activity
Potent disruptor of actin filament function. Alters tight junction permeability. Unlike cytochalasin B, does not inhibit monosaccharide transport across the plasma membrane.
Biochem/physiol Actions
Cell permeable fungal toxin; potent inhibitor of actin polymerization. Disrupts actin microfilaments and activates the p53-dependent pathways causing arrest of the cell cycle at the G1-S transition. Inhibits smooth muscle contraction. Inhibits insulin-stimulated, but not basal, transport of glucose.
Safety Profile
Poison by ingestion,
subcutaneous, and intraperitoneal routes. An
experimental teratogen. Experimental
reproductive effects. Human mutation data
reported. When heated to decomposition it
emits toxic fumes of NOx.
target
p38MAPK | PI3K | Akt | Calcium Channel | ATPase
Background
The fungal-derived toxin Cytochalasin D is a potent inhibitor of actin polymerization, limiting elongation at both the barbed and pointed ends of the actin filament. While several related Cytochalasin toxins bind actin and alter polymerization, Cytochalasin D is the most specific inhibitor of actin microfilaments. The cytoskeleton takes part in signal transduction, protein transport, signal compartmentalization, and cell mobility. Depolymerization of the actin cytoskeleton by Cytochalasin D in mesenchymal stem cells results in localization of G-actin to the nucleus, which leads to mesenchymal stem cell differentiation and bone formation. Treatment of a pair of cancer cell lines with Cytochalasin D results in the inhibition of actin polymerization and decreased cell motility. Treatment of murine CT26 colorectal carcinoma cells with Cytochalasin D inhibited tumor growth through reduced cell proliferation, induction of cell apoptosis, and suppression of tumor angiogenesis.
References
[1] D. GODDETTE C F. Actin polymerization. The mechanism of action of cytochalasin D.[J]. The Journal of Biological Chemistry, 1986, 1 1: 15974-15980. DOI:
10.1016/s0021-9258(18)66662-1[2] S.N RUBTSOVA . Disruption of actin microfilaments by cytochalasin D leads to activation of p53[J]. FEBS Letters, 1998, 430 3: Pages 353-357. DOI:
10.1016/s0014-5793(98)00692-9
