| Celastrol, derived from
trees and shrubs called celastracaea, has been used for centuries in
China to treat symptoms such as fever, chills, joint pain and
inflammation. The MCG researchers think it may also play a role in
cancer treatment by inactivating a protein required for cancer growth.
That protein, P23, is one of many proteins helping the
heat shock protein 90. Scientists are just beginning to realize the
potential of controlling inflammation-related diseases, including
cancer, by inhibiting HSP90.
"Cancer cells need HSP90 more than normal cells
because cancer cells have thousands of mutations," said Dr. Ahmed Chadli,
biochemist in the MCG Center for Molecular Chaperones/Radiobiology and
Cancer Virology. "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."
But most HSP90 inhibitors lack selectivity, disabling
the functions of all proteins activated by HSP90 rather than only the
ones implicated in a specific tumor. Those 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.
"The celastrol induces the protein to form fibrils and
clusters it together, which inactivates it," said Dr. Chadli, whose
research was published in the January edition of The Journal of
Biological Chemistry. "When they are clustered, they're not
available for other functions that help cancer grow."
The research was funded by a seed grant from the MCG
Cardiovascular Discovery Institute and a Scientist Development Grant
from The American Heart Association.
Dr. Chadli envisions future studies on cancer patients
using even more potent derivatives of celastrol.
"They can hopefully be used in combination with other
therapeutic agents to reduce the probability of cancer resistance," he
said. |
