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'Colchicine' is a highly poisonous alkaloid, originally extracted from plants of the genus ''Colchicum'' (Autumn crocus, also known as the "Meadow saffron"). Originally used to treat rheumatic complaints and especially gout, it was also prescribed for its cathartic and emetic effects. Its present medicinal use is mainly in the treatment of gout; as well, it is being investigated for its potential use as an anti-cancer drug. It can also be used as initial treatment for pericarditis and preventing recurrences of the condition.

Contents

History

Pharmacology

Biological function

Colchicine as medicine

Side effects

Toxicity

Botanical use

References

External links

History

Colchicum extract was first described as a treatment for gout in ''De Materia Medica'' by Padanius Dioscorides in the first century CE.
The colchicine alkaloid was first isolated in 1820 by the two French chemists P.S. Pelletier and J. Caventon.^[1]
It was later identified as a tricyclic alkaloid, and its pain-relieving and anti-inflammatory effects for gout were linked to its ability to bind with tubulin.

Pharmacology

Biological function

Colchicine inhibits microtubule polymerization by binding to tubulin, one of the main constituents of microtubules. Availability of tubulin is essential to mitosis, and therefore colchicine effectively functions as a "mitotic poison" or spindle poison.^[2] Since one of the defining characteristics of cancer cells is a significantly increased rate of mitosis, this means that cancer cells are significantly more vulnerable to colchicine poisoning than are normal cells. However, the therapeutic value of colchicine against cancer is (as is typical with chemotherapy agents) limited by its toxicity against normal cells.
Apart from inhibiting mitosis, a process heavily dependent on cytoskeletal changes, colchicine also inhibits neutrophil motility and activity, leading to a net anti-inflammatory effect.

Colchicine as medicine

Colchicine is Food and Drug Administration (FDA)-approved for the treatment of gout and also for familial Mediterranean fever, secondary amyloidosis(AA), and scleroderma.
The Australian biotechnology company Giaconda has developed a combination therapy to treat constipation-predominant irritable bowel syndrome which combines colchicine with the anti-inflammatory drug olsalazine.
Colchicine has a relatively low therapeutic index.
Colchicine is "used widely" off-label by naturopaths for a number of treatments, including the treatment of back pain.^[3]

Side effects

Side effects include gastro-intestinal upset and neutropenia. High doses can also damage bone marrow and lead to anemia. Note that all of these side effects can result from hyper-inhibition of mitosis.

Toxicity

Colchicine poisoning has been compared to arsenic poisoning: symptoms start 2 to 5 hours after the toxic dose has been ingested and include burning in the mouth and throat, fever, vomiting, diarrhea, abdominal pain and kidney failure. Death from respiratory failure can follow. There is no specific antidote for colchicine, although various treatments do exist.

Botanical use

Since chromosome segregation is driven by microtubules, colchicine is also used for inducing polyploidy in plant cells during cellular division by inhibiting chromosome segregation during meiosis; half the resulting gametes therefore contain no chromosomes, while the other half contain double the usual number of chromosomes (''i.e.'', diploid instead of haploid as gametes usually are), and lead to embryos with double the usual number of chromosomes (''i.e.'' tetraploid instead of diploid). While this would be fatal in animal cells, in plant cells it is not only usually well tolerated, but in fact frequently results in plants which are larger, hardier, faster growing, and in general more desirable than the normally diploid parents; for this reason, this type of genetic manipulation is frequently used in breeding plants commercially. In addition, when such a tetraploid plant is crossed with a diploid plant, the triploid offspring will be sterile (which may be commercially useful in itself by requiring growers to buy seed from the supplier) but can often be induced to create a "seedless" fruit if pollinated (usually the triploid will also not produce pollen, therefore a diploid parent is needed to provide the pollen). This is the method used to create seedless watermelons, for instance. On the other hand, colchicine's ability to induce polyploidy can be exploited to render infertile hybrids fertile, as is done when breeding triticale from wheat and rye. Wheat is typically tetraploid and rye diploid, with the triploid hybrid infertile. Treatment with colchicine of triploid triticale gives fertile hexaploid triticale.

References

1. Pelletier PS, Caventon J. Ann. Chim. Phys. 1820;14:69
2. http://biotech.icmb.utexas.edu/botany/colch.html
3. "Deaths sound an Rx alert", ''The Portland Tribune'', Apr 20, 2007

External links

★ Feature on colchicine, by Matthew J. Dowd at vcu.edu