Targeting heat shock protein 90 for anti-cancer drug development

2021 ◽  
Author(s):  
Anthony Aswad ◽  
Tuoen Liu
Keyword(s):  
Heat Shock ◽  
Drug Development ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90 ◽  
Cancer Drug ◽  
Anti Cancer

Secreted Heat Shock Protein-90α: A More Effective and Safer Target for Anti-Cancer Drugs?

2010 ◽  
Vol 5 (2) ◽  
pp. 121-127 ◽  
Author(s):  
Chieh-Fang Cheng ◽  
Jianhua Fan ◽  
Zhengwei Zhao ◽  
David T. Woodley ◽  
Wei Li
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90 ◽  
Cancer Drugs ◽  
Anti Cancer

scholarly journals Heat-shock protein 90 and Cdc37 interact with LKB1 and regulate its stability

2003 ◽  
Vol 370 (3) ◽  
pp. 849-857 ◽  
Author(s):  
Jérôme BOUDEAU ◽  
Maria DEAK ◽  
Margaret A. LAWLOR ◽  
Nick A. MORRICE ◽  
Dario R. ALESSI
Keyword(s):  
Heat Shock ◽  
Protein Kinase ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90 ◽  
Kinase Domain ◽  
Cancer Syndrome ◽  
Hsp90 Inhibitors ◽  
Detailed Mechanism ◽  
Anti Cancer ◽  
Hsp90 Chaperone

LKB1 is a widely expressed serine/threonine protein kinase that is mutated in the inherited Peutz—Jeghers cancer syndrome. Recent findings indicate that LKB1 functions as a tumour suppressor, but little is known regarding the detailed mechanism by which LKB1 regulates cell growth. In this study we have purified LKB1 from cells and establish that it is associated with the heat-shock protein 90 (Hsp90) chaperone and the Cdc37 kinase-specific targetting subunit for Hsp90. We demonstrate that Cdc37 and Hsp90 bind specifically to the kinase domain of LKB1. We also perform experiments using Hsp90 inhibitors, which indicate that the association of Hsp90 and Cdc37 with LKB1 regulates LKB1 stability and prevents its degradation by the proteasome. Hsp90 inhibitors are being considered as potential anti-cancer agents. However, our observations indicate that prolonged usage of these drugs could possibly lead to tumour development by decreasing cellular levels of LKB1.

scholarly journals Spotlight on the microbes that produce heat shock protein 90-targeting antibiotics

Open Biology ◽  
2012 ◽  
Vol 2 (12) ◽  
pp. 120138 ◽  
Author(s):  
Peter W. Piper ◽  
Stefan H. Millson
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Binding Site ◽  
Cancer Progression ◽  
Heat Shock Protein 90 ◽  
Hsp90 Inhibitor ◽  
Cancer Drug ◽  
Atp Binding ◽  
Hsp90 Inhibition ◽  
Atp Binding Site

Heat shock protein 90 (Hsp90) is a promising cancer drug target as a molecular chaperone critical for stabilization and activation of several of the oncoproteins that drive cancer progression. Its actions depend upon its essential ATPase, an activity fortuitously inhibited with a very high degree of selectivity by natural antibiotics: notably the actinomycete-derived benzoquinone ansamycins (e.g. geldanamycin) and certain fungal-derived resorcyclic acid lactones (e.g. radicicol). The molecular interactions made by these antibiotics when bound within the ADP/ATP-binding site of Hsp90 have served as templates for the development of several synthetic Hsp90 inhibitor drugs. Much attention now focuses on the clinical trials of these drugs. However, because microbes have evolved antibiotics to target Hsp90, it is probable that they often exploit Hsp90 inhibition when interacting with each other and with plants. Fungi known to produce Hsp90 inhibitors include mycoparasitic, as well as plant-pathogenic, endophytic and mycorrhizal species. The Hsp90 chaperone may, therefore, be a prominent target in establishing a number of mycoparasitic (interfungal), fungal pathogen–plant and symbiotic fungus–plant relationships. Furthermore the Hsp90 family proteins of the microbes that produce Hsp90 inhibitor antibiotics are able to reveal how drug resistance can arise by amino acid changes in the highly conserved ADP/ATP-binding site of Hsp90.

scholarly journals Detection of the ATPase Activity of the Molecular Chaperones Hsp90 and Hsp72 Using the Transcreener™ ADP Assay Kit

2010 ◽  
Vol 15 (3) ◽  
pp. 279-286 ◽  
Author(s):  
Martin Rowlands ◽  
Craig McAndrew ◽  
Chris Prodromou ◽  
Laurence Pearl ◽  
Andrew Kalusa ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Atpase Activity ◽  
Small Molecule ◽  
Drug Target ◽  
Small Molecule Inhibitors ◽  
Heat Shock Protein 90 ◽  
Cancer Drug ◽  
Cell Growth Inhibition ◽  
Client Proteins

The molecular chaperone heat shock protein 90 (Hsp90) is required for the correct folding and stability of a number of client proteins that are important for the growth and maintenance of cancer cells. Heat shock protein 72 (Hsp72), a co-chaperone of Hsp90, is also emerging as an attractive cancer drug target. Both proteins bind and hydrolyze adenosine triphosphate (ATP), and ATPase activity is essential for their function. Inhibition of Hsp90 ATPase activity leads to the degradation of client proteins, resulting in cell growth inhibition and apoptosis. Several small-molecule inhibitors of the ATPase activity of Hsp90 have been described and are currently being evaluated clinically for the treatment of cancer. A number of methods for the measurement of ATPase activity have been previously used, but not all of these are ideally suited to screening cascades in drug discovery projects. The authors have evaluated the use of commercial reagents (Transcreener™ ADP) for the measurement of ATPase activity of both yeast and human Hsp90 (ATP Km ~500 µM) and human Hsp72 (ATP Km ~1 µM). The low ATPase activity of human Hsp90 and its stimulation by the co-chaperone Aha1 was measured with ease using reduced incubation times, generating robust data (Z′ = 0.75). The potency of several small-molecule inhibitors of both Hsp90 and Hsp72 was determined using the Transcreener™ reagents and compared well to that determined using other assay formats.

scholarly journals Anti-Cancer Properties of Ginkgolic Acids in Human Nasopharyngeal Carcinoma CNE-2Z Cells via Inhibition of Heat Shock Protein 90

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6575
Author(s):  
Hong-Mei Li ◽  
Hui Ma ◽  
Xiaolong Sun ◽  
Bohan Li ◽  
Chengjiang Cao ◽  
...  
Keyword(s):  
Heat Shock ◽  
Nasopharyngeal Carcinoma ◽  
Heat Shock Protein ◽  
Human Cancer ◽  
Heat Shock Protein 90 ◽  
Migration And Invasion ◽  
Hsp90 Inhibitors ◽  
Human Nasopharyngeal Carcinoma ◽  
Anti Cancer ◽  
Ginkgolic Acids

Ginkgo biloba L. has been used in traditional Chinese medicine (TCM) for thousands of years. However, the anti-cancer properties of ginkgolic acids (GAS) isolated from G. biloba have not been investigated in human nasopharyngeal carcinoma cells. In this study, GAS exhibited an inhibitory effect on the ATPase activity of heat shock protein 90 (Hsp90) and anti-proliferative activities against four human cancer cell lines, with IC50 values ranging from 14.91 to 23.81 μg·mL−1. In vivo experiments confirmed that GAS inhibited tumor growth in CNE-2Z cell-xenografted nude mice with low hepatotoxicity. We further demonstrated that GAS suppressed migration and invasion and induced the apoptosis of CNE-2Z cells by inducing the degradation of Hsp90 client proteins (MMP-2, MMP-9, Her-2, c-Raf, Akt, and Bcl-2). Together, GAS are new Hsp90 inhibitors by binding to Hsp90 (hydrogen bond and hydrophobic interaction). Thus, GAS from G. biloba might represent promising Hsp90 inhibitors for the development of anti-nasopharyngeal carcinoma agents.

Glycyrrhizin effects rat hepatocytes via the reduction of heat shock protein 90 expression

2001 ◽  
Vol 120 (5) ◽  
pp. A357-A357
Author(s):  
T YOH ◽  
T NAKASHIMA ◽  
Y SUMIDA ◽  
Y KAKISAKA ◽  
H ISHIKAWA ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90 ◽  
Rat Hepatocytes

430: Modulation of Heat-Shock Protein 90 (HSP90) Client Protein Expression in Prostate Cancer Cells by a Novel Novobiocin Analog

2006 ◽  
Vol 175 (4S) ◽  
pp. 140-140
Author(s):  
Manlio A. Goetzl ◽  
Brian S. Blagg ◽  
Benjamin Cronk ◽  
Len Neckers ◽  
Jeffrey M. Holzbeierlein
Keyword(s):  
Prostate Cancer ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Protein Expression ◽  
Cancer Cells ◽  
Heat Shock Protein 90 ◽  
Client Protein ◽  
Prostate Cancer Cells ◽  
Hsp90 Client Protein
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