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.
'In the future, this research could have applications in other cancers'
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."
"In the future, this research could have applications in drug development for hormone-dependent cancers, including breast, prostate and endometrial cancers," he said.
"One of the major areas of scientific emphasis of the GRU Cancer Center is to develop therapeutic approaches to cancer targeting specific molecules within the cancer cell, including chaperones," added Dr. Samir N. Khleif, director of the GRU Cancer Center. "This finding is an important piece of the puzzle, bringing us closer to our goal of helping patients with cancer."
Gedunin, according to Santa Cruz Biotechnology, Inc., "is a naturally occurring Hsp90 inhibitor. In vitro, Gedunin induces Hsp90-dependent client protein degradation and displays antiproliferative activity."
It is obtained from the Indian neem tree and has been used for centuries in Asia as a natural remedy for malaria. It has also been used as an insecticidal and, most recently, as an anti-cancer agent.
Gedunin may be useful in treatment of neurological disorders too
In 2009, researchers found a nearly 80 percent decrease in the cell proliferation in ovarian cancer cells after in-vitro treatment with gedunin. (http://saypeople.com)
A separate study by Emory University found that gedunin and its derivatives looked promising in the treatment of Parkinson's disease, Alzheimer's disease, HIV-related dementia, multiple sclerosis, amyotrophic lateral sclerosis, stroke, and Huntington's disease.
As for Chadli, he says that this research could have applications in drug development for hormone-dependent cancers, including breast, prostate, and endometrial cancers.
Sources:
http://www.eurekalert.org/pub_releases/2013-02/ghsu-ipc021413.php
http://www.scbt.com/datasheet-203967-gedunin.html
http://saypeople.com
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Source: http://www.naturalnews.com/039224_cancer_cells_plant_medicine_Hsp90.html
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