Planta Med 2015; 81(14): 1223-1239
DOI: 10.1055/s-0035-1546251
Reviews
Georg Thieme Verlag KG Stuttgart · New York

Hsp90 Activity Modulation by Plant Secondary Metabolites

Fabrizio Dal Piaz
1   Dipartimento di Farmacia, Università di Salerno, Fisciano (SA), Italy
,
Stefania Terracciano
1   Dipartimento di Farmacia, Università di Salerno, Fisciano (SA), Italy
,
Nunziatina De Tommasi
1   Dipartimento di Farmacia, Università di Salerno, Fisciano (SA), Italy
,
Alessandra Braca
2   Dipartimento di Farmacia, Università di Pisa, Pisa, Italy
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 30. Dezember 2014
revised 13. Mai 2015

accepted 30. Mai 2015

Publikationsdatum:
30. Juli 2015 (online)

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Abstract

Hsp90 is an evolutionarily conserved adenosine triphosphate-dependent molecular chaperone and is one of the most abundant proteins in the cells (1–3 %). Hsp90 is induced when a cell undergoes various types of environmental stresses such as heat, cold, or oxygen deprivation. It is involved in the turnover, trafficking, and activity of client proteins, including apoptotic factors, protein kinases, transcription factors, signaling proteins, and a number of oncoproteins. Most of the Hsp90 client proteins are involved in cell growth, differentiation, and survival, and include kinases, nuclear hormone receptors, transcription factors, and other proteins associated with almost all the hallmarks of cancer. Consistent with these diverse activities, genetic and biochemical studies have demonstrated the implication of Hsp90 in a range of diseases, including cancer, making this chaperone an interesting target for drug research.

During the last few decades, plant secondary metabolites have been studied as a major source for lead compounds in drug discovery. Recently, several plant-derived small molecules have been discovered exhibiting inhibitory activity towards Hsp90, such as epigallocatechin gallate, gedunin, lentiginosine, celastrol, and deguelin. In this work, an overview of plant secondary metabolites interfering with Hsp90 activities is provided.