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What Is Thapsigargin?

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  • Written By: Canaan Downs
  • Edited By: A. Joseph
  • Last Modified Date: 05 November 2016
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The thapsia plant is the only known natural source of thapsigargin, a chemical that is believed by some to shed light into the mechanism of action of one of the most powerful malaria treatments that has been discovered. Although it is known to encourage the development of tumors in mammals, it might prove to be a useful treatment for posterior capsular opacification, or recurring cataracts. The most common use for the chemical is as an experimental agent for research into the effects of increasing calcium ion concentration in mammalian cellular fluid.

Thapsigargin acts on these cells by interfering with the operation of their calcium ion pumps, reducing the amount of the ion in endoplasmic and sarcoplasmic reticula. This triggers the cells to activate plasma membrane calcium ion channels, increasing the calcium ion concentration of the cellular fluid. This action promotes the development of tumors in affected cells, which might explain the toxicity of related chemicals.

The malaria medication artemisinin, also known as qinghaosu, is a member of the same chemical class as thapsigargin. These chemicals are both sesquiterpene lactones, an incredibly bitter set of pharmacologically active compounds found predominantly in plants of the Artemisia genus. The structural similarity of thapsigargin to artemisinin has led some researchers to propose that the efficacy of the anti-malarial medication might be because of its promotion of tumors in the malarial parasite Plasmodium falciparum.

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If artemisinin does share the same mechanism, then it exerts its toxic effects on the parasite by its inhibition of an enzyme called sarco/endoplasmic reticulum Ca2+ ATP-ase (SERCA). By increasing cytosolic calcium levels in the rapidly dividing malarial parasite, artemisinin could promote the development of fatal malignancies within the organism. As of early 2011, though, there was no research that confirmed that artemisinin shares anything more than a superficial structural similarity with thapsigargin.

Despite its known activity as a tumor-promoting agent, one study suggests that the use of contact lenses treated with an extended-release form of thapsigargin could effectively inhibit the development of the cells responsible for the post-operative recurrence of cataracts. As many as 50 percent of patients who have their cataracts surgically removed develop posterior capsular ossification within months of the treatment, making further surgery necessary to restore their sight. Although the extensive laser treatments widely used to treat this condition might not be practical in the developing world, thapsigargin-embedded lenses could help prevent cataract relapse in patients who would otherwise be unable to afford follow-up surgeries.

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