Monday, February 8, 2010

Celastrol Inhibiting Hsp90 Chaperoning - a new way to treat cancer?

Celastrol, derived from trees and shrubs called celastracaea,  (Thunder of God Vine) has been used for centuries in China to treat symptoms such as fever, chills, joint pain and inflammation.Celastrol has been shown to possess antioxidant, anti-inflammatory activities. The same compound has been tried for Alzheimer's disease and anticancer activity  also.

Now Dr. Ahmed Chadli, has come up with an interesting findings i.e., Celastrol may play a role in cancer treatment by inactivating a protein required for cancer growth.  Protein, P23, is one of many proteins helping the heat shock protein 90. Dr. Chadli claims that,  "scientists are just beginning to realize the potential of controlling inflammation-related diseases, including cancer, by inhibiting HSP90".

As per  claim by Dr. Chadli, cancer cells need HSP90 more than normal cells because cancer cells have thousands of mutations. 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

Most HSP90 inhibitors lack selectivity, disabling the functions of all proteins activated by HSP90 rather than only the ones implicated in a specific tumor and proteins vary from one tumor to another. Dr. Chadli and colleagues at the Mayo Clinic believe celastrol holds the key to specificity, targeting the HSP90-activated protein required for folding steroid receptors.

Celastrol inhibits the Hsp90 chaperoning machinery by inactivating the co-chaperone p23, resulting in a more selective destabilization of steroid receptors compared with kinase clients. Both in vitro and in vivo results demonstrate that celastrol disrupts p23 function by altering its three-dimensional structure, leading to rapid formation of amyloid-like fibrils. This study reveals a unique inhibition mechanism of p23 by a small molecule that could be exploited in the dissection of protein fibrillization processes as well as in the therapeutics of steroid receptor-dependent diseases....

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