The Plant Derivative Celastrol Prompts Cancer Cells to Self-Destruct

Celastrol, an anti-inflammatory plant derivative long used in Chinese medicine, has been found to have potential as an anticancer drug due to its ability to inhibit the procancer protein p23.

Investigators at the Medical College of Georgia (Augusta, USA) were studying the effect of celastrol on the heat shock protein HSP90, a key modulator of the inflammatory response and linked to both autoimmune diseases and cancer.

They reported in the February 5, 2010, issue of the Journal of Biological Chemistry that celastrol inhibited the Hsp90 chaperoning machinery by inactivating the cochaperone p23, resulting in selective destabilization of steroid receptors. In vitro and in vivo results demonstrated that celastrol disrupted p23 function by altering its three-dimensional structure, leading to rapid formation of amyloid-like fibrils.

"The celastrol induces the protein to form fibrils and clusters it together, which inactivates it,” explained senior author Dr. Ahmed Chadli, professor of biochemistry at the Medical College of Georgia. "When they are clustered, they are not available for other functions that help cancer grow."

"Cancer cells need HSP90 more than normal cells because cancer cells have thousands of mutations,” said Dr. Chadli. "They need chaperones all the time to keep their mutated proteins active. By taking heat shock proteins away from cells, the stabilization is taken away and cell death occurs.”

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