Papers of the Week

Indian Medicinal Plant Compound as a Potential Cancer Drug

See referenced article, J. Biol. Chem. 2013, 288, 73137325 Gedunin Inactivates the Co-chaperone p23 Protein Causing Cancer Cell Death by Apoptosis

The chaperone protein Hsp90 is a potential cancer drug target, but to date, the clinical efficacy of Hsp90 inhibitors has been suboptimal. In this Paper of the Week, a team led by Ahmed Chadli at the Georgia Regents University demonstrated that the natural plant product gedunin, which is used to treat malaria and other infectious diseases in traditional Indian medicine, may be able to stall the Hsp90 machinery. The investigators demonstrated that gedunin binds p23, a co-chaperone to Hsp90. The gedunin binding prevents p23 from partnering with Hsp90 and stops them from inducing the overexpression of anti-apoptotic proteins Hsp70 and Hsp27. By using molecular docking along with mutational and functional analysis, the investigators showed that gedunin inhibits p23 chaperoning activity, blocks its interaction with Hsp90, and interBinding of gedunin destabilizes steroid receptor (SR)-chapcomplexes, leading to proteasomal degradation of steroid feres with p23-mediated gene regulation. erone receptors. p23 bound to gedunin is cleaved more efficiently by The authors say, These results provide im- the activated caspase-7, which promotes apoptotic cell death. portant insight into the molecular mechanism of action of this promising lead compound. DOI 10.1074/jbc.P112.427328 7326