Researchers at the Georgia Regents University Cancer Center have identified an India-based plant which has been used for centuries to treat inflammation, fever and malaria that could be used to help kill cancer cells.
Dr. Ahmed Chadli, a researcher in the Molecular Chaperone Program at the GRU Cancer Center and senior author of the study named the Journal of Biological Chemistry's "Paper of the Week," said cancer cells typically survive by hijacking so-called molecular chaperones that in turn guide and protect the proteins that ensure normal cellular function, then tricking them into assisting mutated versions of those proteins to stay alive, according to a press release published by the university.
Therefore, development of drugs has focused largely on the chaperone Hsp90 (heat shock protein 90) "because it plays a key role in assisting mutating proteins, making it an attractive cancer drug target," the release said.
But the clinical efficacy of Hsp90 inhibitors has been less than stellar; most current small molecules that target Hsp90 have inadvertently resulted in the expression of proteins that protect cancerous cells from cell death, thereby compromising the Hsp90 inhibitors in the clinical setting.
In the current study; however, Chaitanya Patwardhad, a graduate student in Dr. Chadli's laboratory, discovered that gedunin, an Indian plant compound, attacks a helper protein, or co-chaperone, of Hsp90 known as p23.
"This compound binds directly to p23, leading to inactivation of the Hsp90 machine - without production of anti-apoptotic proteins - thus killing cancer cells," said Chadli. "The idea here is that this will open a door for new ways of targeting Hsp90 by targeting its helper proteins, which may be used in combination with established Hsp90 inhibitors that are ongoing clinical trials."
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