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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]
Whether colchicine is safe for use during pregnancy is unclear, but its use during breastfeeding appears to be safe. [11] [15] Colchicine works by decreasing inflammation via multiple mechanisms. [16] Colchicine, in the form of the autumn crocus (Colchicum autumnale), was used as early as 1500 BC to treat joint swelling. [17]
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.
Microtubule and tubulin metrics [1]. Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm [2] and have an inner diameter between 11 and 15 nm. [3]
Drugs such as colchicine and vinblastine, which block assembly of microtubules, freely cross the membrane into the cytosol, but the export of these drugs by ABCB1 reduces their concentration in the cell. Therefore, it takes a higher concentration of the drugs is required to kill the cells that express ABCB1 than those that do not express the gene.
It is closely related to the natural alkaloid colchicine with the replacement of the acetyl group on the amino moiety with methyl, but it is less toxic. It depolymerises microtubules and limits microtubule formation (inactivates spindle fibre formation), thus arresting cells in metaphase and allowing cell harvest and karyotyping to be performed.
The primary pathway by which microtubule nucleation is assisted requires the action of a third type of tubulin, γ-tubulin, which is distinct from the α and β subunits that compose the microtubules themselves. The γ-tubulin combines with several other associated proteins to form a conical structure known as the γ-tubulin ring complex (γ-TuRC).
We now know these fibers are microtubules. By perturbing cells with agents that cause microtubules to depolymerize (e.g. colchicine or high pressure) or polymerize excessively (e.g. D 2 O), Inoué demonstrated that spindle fibers are in a state of rapid dynamic equilibrium with a pool of soluble subunits in the cytoplasm. He went on to show ...