New Drug Causes Cancer Cells To Fill With Garbage, Self Destruct

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A promising new cancer treatment targets a cancer cell’s proteasome, causing the cell to self-destruct.

A proteasome is a hollow, cylindrical cell organelle that works much like a kitchen garbage disposal. Proteins that are tagged as defective enter through openings on either end of the proteasome, and are then “chewed up” and disposed of.

Rapidly reproducing cancer cells are usually teeming with genetic mutations, leading to the production of many faulty proteins that need to be tagged and tossed. The new cancer compound inhibits the proteasome disposal mechanism so that cells become bloated with the defective proteins, and die.

The tag that marks proteins as defective is made of at least four copies of the tiny protein ubiquitin. A part of the proteasome called Rpn11 normally cuts the ubiquitin tag off the defective protein as it enters a proteasome because the tag is too large to fit inside.

The innovative treatment works by preventing the Rpn11 from cutting off the ubiquitin tag, making it impossible for the dysfunctional proteins to enter the proteasome. With its disposal mechanism disabled, a cell’s defective proteins accumulate to catastrophic levels, leading to the cell’s demise.

Though the experimental compound affects the proteasomes of all cells, normal cells are believed to have fewer flawed proteins than diseased cells. Having more defective proteins makes cancer cells susceptible to the effects of proteasome inhibition, so even a small dose can be fatal.

Current cancer drugs that target cell protein disposal work inside the proteasome, and tend to lose efficacy over time. “Our research offers an alternative path to disabling proteasome function, including in cells that no longer respond to the existing drugs,” said researcher and postdoctoral scholar, Jing Li.

The new compound has so far been tested on human cancer cells in the laboratory by researchers associated with Caltech. Their study was published online in Nature Chemical Biology.

Source: Science Daily

 

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