Snapshot Issue 26 September 2006

Chlorotoxin

Written by Giuliana Brunetti

Finding the intruder is the oncologist's puzzle when searching for new anti-tumour drugs. To be effective, tumour treatments must be able to distinguish cancerous cells from healthy cells, so as to kill them off without damaging healthy tissue. And what – in this kind of hunt – is better than a scorpion called “Death Stalker”? Though the scorpion won its nick name for other kinds of prey in the Israeli desert, today the Egyptian scorpion - Leiurus quinquestriatus - is winning fame for its powerful venom components in the targeting of cancerous cells.

The Egyptian scorpion's venom is injected via a sting, and can kill animals bigger than the arthropod itself by bringing on heart or respiratory failure following symptoms such as convulsions, or increased heart rate and blood pressure. The two main compounds to cause such distress are the neurotoxins chlorotoxin and charbydotoxin. Both toxins bind to channels on the nerve cell membranes causing neurological dysfunction and subsequent death.

Such toxins are of great interest for developing anti-tumour drugs. Indeed, chlorotoxin has shown promise for anti-tumour activity. How? Chlorotoxin is a 36 amino-acid peptide that binds with a high affinity to calcium-activated chloride channels. And it so happens that this kind of channel is over-expressed in a number of cancers, amongst which gliomas. Recently, a synthetic version of chlorotoxin called TM-601 was tested in patients with severe glioma. However, at such a dose TM-601 cannot kill on its own, so it is used as a vector for the real killer: radioactive iodine.

So far the results seem to be encouraging. It is not the first time a natural poison is used as a drug: purple foxglove glycosides are used to treat heart disease, bacterial toxin botulin is used for muscle spasms and snailfish venom is used as a painkiller. Let us hope that chlorotoxin is one of the pieces of the puzzle the oncologists seek.

Chlorotoxin, Leiurus quinquestriatus quinquestriatus (Egyptian scorpion): P45639

L'édition française de cette chronique est disponible dans l'Instantanés du mois de Prolune.

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