Regulating the cytoprotective response in cancer cells using simultaneous inhibition of Hsp90 and Hsp70

2015 ◽  
Vol 13 (7) ◽  
pp. 2108-2116 ◽  
Author(s):  
Y. Wang ◽  
S. R. McAlpine
Keyword(s):  
Heat Shock ◽  
Cell Growth ◽  
Heat Shock Protein ◽  
Cancer Cells ◽  
Cell Function ◽  
Heat Shock Protein 90 ◽  
Simultaneous Inhibition ◽  
Cytoprotective Response

Both heat shock protein 90 and 70 (Hsp90, Hsp70) are cytoprotective proteins that regulate cell function and faciliate cell growth by stabilizing and folding proteins.

scholarly journals Novel Heat Shock Protein 90 Inhibitors Suppress P-Glycoprotein Activity and Overcome Multidrug Resistance in Cancer Cells

2019 ◽  
Vol 20 (18) ◽  
pp. 4575 ◽  
Author(s):  
Jelena Dinić ◽  
Ana Podolski-Renić ◽  
Mirna Jovanović ◽  
Loana Musso ◽  
Ivanka Tsakovska ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Heat Shock ◽  
Cell Growth ◽  
Heat Shock Protein ◽  
Cancer Cells ◽  
Heat Shock Protein 90 ◽  
Dependent Manner ◽  
Hsp90 Inhibitors ◽  
Relationship Analysis ◽  
P Glycoprotein

Heat Shock Protein 90 (Hsp90) chaperone interacts with a broad range of client proteins involved in cancerogenesis and cancer progression. However, Hsp90 inhibitors were unsuccessful as anticancer agents due to their high toxicity, lack of selectivity against cancer cells and extrusion by membrane transporters responsible for multidrug resistance (MDR) such as P-glycoprotein (P-gp). Recognizing the potential of new compounds to inhibit P-gp function and/or expression is essential in the search for effective anticancer drugs. Eleven Hsp90 inhibitors containing an isoxazolonaphtoquinone core were synthesized and evaluated in two MDR models comprised of sensitive and corresponding resistant cancer cells with P-gp overexpression (human non-small cell lung carcinoma and colorectal adenocarcinoma). We investigated the effect of Hsp90 inhibitors on cell growth inhibition, P-gp activity and P-gp expression. Structure–activity relationship analysis was performed in respect to cell growth and P-gp inhibition. Compounds 5, 7, and 9 directly interacted with P-gp and inhibited its ATPase activity. Their potential P-gp binding site was identified by molecular docking studies. In addition, these compounds downregulated P-gp expression in MDR colorectal carcinoma cells, showed good relative selectivity towards cancer cells, while compound 5 reversed resistance to doxorubicin and paclitaxel in concentration-dependent manner. Therefore, compounds 5, 7 and 9 could be promising candidates for treating cancers with P-gp overexpression.

Effect of Heat Shock Protein 90 (Hsp90) on Migration and Invasion of Human Cancer Cells in Vitro

2014 ◽  
Vol 157 (4) ◽  
pp. 476-478 ◽  
Author(s):  
A. V. Snigireva ◽  
V. V. Vrublevskaya ◽  
Yu. Yu. Skarga ◽  
Yu. V. Evdokimovskaya ◽  
O. S. Morenkov
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Cancer Cells ◽  
Human Cancer ◽  
Heat Shock Protein 90 ◽  
Migration And Invasion ◽  
Human Cancer Cells

Overexpression of human 27 kDa heat shock protein in laryngeal cancer cells confers chemoresistance associated with cell growth delay

2006 ◽  
Vol 133 (1) ◽  
pp. 37-46 ◽  
Author(s):  
Jung-Hee Lee ◽  
Dongil Sun ◽  
Kwang-Jae Cho ◽  
Min-Sik Kim ◽  
Myung-Hwa Hong ◽  
...  
Keyword(s):  
Heat Shock ◽  
Cell Growth ◽  
Heat Shock Protein ◽  
Cancer Cells ◽  
Laryngeal Cancer ◽  
Growth Delay
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