Heat Shock Protein Inhibitor a Potential Chemotherapeutic Agent

These stresses normally act to damage proteins, causing partial unfolding and possible aggregation. By temporarily binding to hydrophobic residues exposed by stress, Hsp70 prevents these partially denatured proteins from aggregating, and allows them to refold. HSP70 expression is elevated in many cancers, contributing to tumor cell survival and resistance to therapy.

Investigators at the University of Pennsylvania School of Medicine (Philadelphia, USA) identified a small molecule, 2-phenylethynesulfonamide (PES) that interacted selectively with HSP70 and led to a disruption of the association between HSP70 and several of its cochaperone and substrate proteins.

Data published in the October 9, 2009, issue of the journal Molecular Cell revealed that treatment of cultured tumor cells with PES promoted cell death that was associated with protein aggregation, impaired autophagy, and inhibition of lysosomal function. Furthermore, PES was able to suppress tumor development and enhance survival in a mouse model.

Senior author Dr. Donna George, associate professor of genetics at the University of Pennsylvania School of Medicine, said, "It is still early days, we do not know what it will do in a human. But, the exciting part is that this is a pathway and a protein target that clearly is important for cancer cells."

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University of Pennsylvania School of Medicine