Drug development has focused on the chaperone Hsp90 - heat shock protein 90 because it plays a key role in assisting mutated proteins, making it an attractive cancer drug target.
However, the clinical efficacy of Hsp90 inhibitors has been disappointing, according to the study published in the Journal of Biological Chemistry.Most current small molecules targeting Hsp90 have inadvertently resulted in the expression of proteins that protect cancer cells from programmed cell death and compromise the Hsp90 inhibitors in the clinic.
In this study, however, Chaitanya Patwardhan, a graduate student in Chadli's lab, found that gedunin, compound from the Indian plant 'neem', attacks a co-chaperone, or helper protein, of Hsp90 called p23. "This compound binds directly to p23, leading to inactivation of the Hsp90 machine without production of anti-apoptotic proteins - thus killing cancer cells," Chadli said in a statement."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," said Chadli.
"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," said 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," said Khleif.
(Agencies)
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Tags: neem, neem trees, cancer cells, Neem to cure disease
M. D. Hegde
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