March 11, 2013
The chaperone protein Hsp90 is a potential cancer drug target but to date, the clinical efficacy of Hsp90 inhibitors has been less than satisfactory. In a recent Paper of the Week in the Journal of Biological Chemistry, a team led by Ahmed Chadli at the Georgia Regents University demonstrated that the natural plant product, gedunin, may be able to stall the Hsp90 machinery.
Gedunin comes from the neem tree extracts. The plant extracts have been used to treat malaria and other infectious diseases in traditional Indian medicine.
Chadli and colleagues demonstrated that gedunin could potentially also be used for cancer therapies. In their work, the investigators showed that the molecule binds p23, a co-chaperone to Hsp90. The gedunin binding prevents p23 from partnering with Hsp90 and stops them from inducing the overexpression of antiapoptotic proteins, Hsp70 and Hsp27. By using molecular docking along with mutational and functional analysis, the investigators provided evidence that gedunin inhibits p23 chaperoning activity, blocks its interaction with Hsp90 and interferes with p23-mediated gene regulation.
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