Identification of heat shock protein 90 inhibitors to sensitize drug resistant side population tumor cells using a cell based assay platform

2012 ◽  
Vol 317 (1) ◽  
pp. 78-88 ◽  
Author(s):  
Praveen K. Sobhan ◽  
Mahendra Seervi ◽  
Jeena Joseph ◽  
Bhavya Balan Chandrika ◽  
Saneesh Varghese ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Tumor Cells ◽  
Side Population ◽  
Heat Shock Protein 90 ◽  
Drug Resistant ◽  
A Cell

scholarly journals Heat Shock Protein-90 Inhibitors Enhance Antigen Expression on Melanomas and Increase T Cell Recognition of Tumor Cells

PLoS ONE ◽  
2014 ◽  
Vol 9 (12) ◽  
pp. e114506 ◽  
Author(s):  
Timothy J. Haggerty ◽  
Ian S. Dunn ◽  
Lenora B. Rose ◽  
Estelle E. Newton ◽  
Franco Pandolfi ◽  
...  
Keyword(s):  
T Cell ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Tumor Cells ◽  
Heat Shock Protein 90 ◽  
Antigen Expression ◽  
Cell Recognition ◽  
T Cell Recognition

scholarly journals Preferential Sensitization of Tumor Cells to Radiation by Heat Shock Protein 90 Inhibitor Geldanamycin

2005 ◽  
Vol 46 (2) ◽  
pp. 215-221 ◽  
Author(s):  
Yoshitaka MATSUMOTO ◽  
Hikaru MACHIDA ◽  
Nobuo KUBOTA
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Tumor Cells ◽  
Heat Shock Protein 90

scholarly journals Thermosensitization of tumor cells with inhibitors of chaperone activity and expression

2012 ◽  
Vol 58 (6) ◽  
pp. 662-672 ◽  
Author(s):  
V.A. Kudryavtsev ◽  
Y.M. Makarova ◽  
A.E. Kabakov
Keyword(s):  
Cell Death ◽  
Heat Stress ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Tumor Cells ◽  
De Novo ◽  
Heat Shock Protein 90 ◽  
Chaperone Activity ◽  
Hsp90 Activity ◽  
Hsp90 Chaperone

Effects of inhibitors of the heat shock protein 90 (HSP90) chaperone activity and inhibitors of the heat shock protein (HSP) expression on sensitivity of HeLa tumor cells to hyperthermia were studied. It was found that nanomolar concentrations of inhibitors of the HSP90 activity (17AAG or radicicol) slowed down chaperone-dependent reactivation of a thermo-labile reporter (luciferase) in heat-stressed HeLa cells and slightly enhanced their death following incubation for 60 min at 43°C. Herein, the inhibitors of HSP90 activity stimulated de novo induction of additional chaperones (HSP70 and HSP27) that significantly increased the intracellular HSP levels. If the cells were treated with 17AAG or radicicol along with an inhibitor of the HSP induction (e.g. quercetin or triptolid, or NZ28), this fully prevented the increase in intracellular chaperone levels resulting from the inhibition of HSP90 activity and subsequent heating. Importantly, in the case of conjunction of all the three treatments (an inhibitor of the HSP90 activity + an inhibitor of the HSP induction + 43°C for 60 min), the reporter reactivation was retarded yet stronger while the cell death was sharply (2-3-fold) enhanced. Such an enhancement of the cytotoxicity appears to occur owing to the "chaperone deficiency" when prior to heat stress both the functional activity of constitutive HSP90 and the expression of additional (inducible) chaperones are blocked in the cells.

The Mechanisms of Stimulation of Migration and Invasion of Tumor Cells by Extracellular Heat Shock Protein 90 (eHsp90) in vitro

BIOPHYSICS ◽  
2018 ◽  
Vol 63 (6) ◽  
pp. 931-939
Author(s):  
A. V. Snigireva ◽  
V. V. Vrublevskaya ◽  
M. A. Zhmurina ◽  
Y. Y. Skarga ◽  
O. S. Morenkov
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Tumor Cells ◽  
Heat Shock Protein 90 ◽  
Migration And Invasion ◽  
Stimulation Of

scholarly journals Antitumor Activity of SNX-2112, a Synthetic Heat Shock Protein-90 Inhibitor, in MET-Amplified Tumor Cells with or without Resistance to Selective MET Inhibition

2011 ◽  
Vol 17 (1) ◽  
pp. 122-133 ◽  
Author(s):  
Thomas Bachleitner-Hofmann ◽  
Mark Y. Sun ◽  
Chin-Tung Chen ◽  
David Liska ◽  
Zhaoshi Zeng ◽  
...  
Keyword(s):  
Heat Shock ◽  
Antitumor Activity ◽  
Heat Shock Protein ◽  
Tumor Cells ◽  
Heat Shock Protein 90

scholarly journals Bortezomib enhances dendritic cell (DC)–mediated induction of immunity to human myeloma via exposure of cell surface heat shock protein 90 on dying tumor cells: therapeutic implications

Blood ◽  
2007 ◽  
Vol 109 (11) ◽  
pp. 4839-4845 ◽  
Author(s):  
Radek Spisek ◽  
Anna Charalambous ◽  
Amitabha Mazumder ◽  
David H. Vesole ◽  
Sundar Jagannath ◽  
...  
Keyword(s):  
Cell Death ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Antitumor Immunity ◽  
Heat Shock Protein 90 ◽  
Human Tumors ◽  
Tumor Cell Death ◽  
Dying Cells

Abstract Most anticancer chemotherapies are immunosuppressive and induce nonimmunogenic tumor cell death. Bortezomib, a specific inhibitor of 26S proteasome, has shown clinical activity in several human tumors, including myeloma. Here we show that the uptake of human myeloma cells by dendritic cells (DCs) after tumor cell death by bortezomib, but not γ irradiation or steroids, leads to the induction of antitumor immunity, including against primary tumor cells, without the need for any additional adjuvants. The delivery of activating signal from bortezomib-killed tumor cells to DCs depends on cell-cell contact between DCs and dying tumor cells and is mediated by bortezomib-induced exposure of heat shock protein 90 (hsp90) on the surface of dying cells. The combination of bortezomib and geldanamycin (an hsp90 inhibitor) leads to greater apoptosis of tumor cells but abrogates their immunogenicity. These data identify drug-induced exposure of endogenous heat shock proteins on the surface of dying cells as a mechanism of immunogenic death of human tumors. Specific targeting of bortezomib to tumors may enhance their immunogenicity and the induction of antitumor immunity.

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