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Colchicine is a medication used to prevent and treat gout, [3] [4] to treat familial Mediterranean fever [5] and Behçet's disease, [6] and to reduce the risk of myocardial infarction. [7] The American College of Rheumatology recommends colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs) or steroids in the treatment of gout.
Colchicine is known to inhibit cell division and proliferation. Early study demonstrated that colchicine disrupts the mitotic spindle. Dissolution of microtubules subsequently was shown to be responsible for the effect of colchicine on the mitotic spindle and cellular proliferation. [27]
These stabilized microtubules accumulate post-translational modifications on their tubulin subunits by the action of microtubule-bound enzymes. [40] [41] However, once the microtubule depolymerizes, most of these modifications are rapidly reversed by soluble enzymes. Since most modification reactions are slow while their reverse reactions are ...
Cytoskeletal drugs are small molecules that interact with actin or tubulin.These drugs can act on the cytoskeletal components within a cell in three main ways. Some cytoskeletal drugs stabilize a component of the cytoskeleton, such as taxol, which stabilizes microtubules, or Phalloidin, which stabilizes actin filaments.
Colchicine binds to β- tubulin and forms tubulin-colchicine complexes. [ 5 ] [ 6 ] These complexes interfere with microtubule formation microtubules. Low doses of colchicine can inhibit the formation of microtubules, while high doses depolymerize or break down a polymer to a monomer. [ 7 ]
Microtubules are assembled from dimers of α- and β-tubulin. These subunits are slightly acidic, with an isoelectric point between 5.2 and 5.8. [14] Each has a molecular weight of approximately 50 kDa. [15] To form microtubules, the dimers of α- and β-tubulin bind to GTP and assemble onto the (+) ends of microtubules while in the GTP-bound ...
Microtubules are particularly important as they sense mechanical forces and transmit these signals within the cell. Disruption of microtubules using drugs like colchicine completely inhibits tendril coiling in Pisum sativum , demonstrating their essential role in responding to mechanical cues. [ 6 ]
Because microtubules are involved in cell division, signal transduction and regulation of gene expression, colchicine can inhibit cell division and inflammatory processes (e.g. action of neutrophils and leukocytes). [36] It is suggested that colchicine inhibit chemotactic activity of leukocytes, which leads to reduction of pachydermia. [37]