Natural heat shock protein 90 inhibitors in cancer and inflammation

Abstract

Heat shock protein (HSP)90 is the most abundant HSPs, which are chaperone molecules whose major roles are cell protection and maintenance by means of aiding the folding, the stabilization and the remodeling of a wide range of proteins. A few hundreds of proteins depend on HSP90 chaperone activity, including kinases and transcriptional factors that play essential roles in cancer and inflammation, so that HSP90-targeted therapies have been considered as a potential strategy for the treatment of cancer and inflammatory-associated diseases. HSP90 inhibition by natural, semi-synthetic and synthetic compounds have yield promising results in pre-clinical studies and clinical trials for different types of cancers and inflammation. Natural products are a huge source of biologically active compounds widely used in drug development due to the great diversity of their metabolites which are capable to modulate several protein functions. HSP90 inhibitors have been isolated from bacteria, fungi and vegetal species. These natural compounds have a noteworthy ability to modulate HSP90 activity as well as serve as scaffolds for the development of novel synthetic or semi-synthetic inhibitors. Over a hundred clinical trials have evaluated the effect of HSP90 inhibitors as adjuvant treatment against different types of tumors and, currently, new studies are being developed to gain sight on novel promising and more effective approaches for cancer treatment. In this review, we present the naturally occurring HSP90 inhibitors and analogues, discussing their anti-cancer and anti-inflammatory effects.

Keywords: Cancer; HSP90; Inflammation; Natural products.