scholarly journals Disulfiram/copper causes redox-related proteotoxicity and concomitant heat shock response in ovarian cancer cells that is augmented by auranofin-mediated thioredoxin inhibition

Oncoscience ◽  
2013 ◽  
Vol 1 (1) ◽  
pp. 21-29 ◽  
Author(s):  
Margarita Papaioannou ◽  
Ioannis Mylonas ◽  
Richard E. Kast ◽  
Ansgar Bruning
Keyword(s):  
Ovarian Cancer ◽  
Heat Shock ◽  
Cancer Cells ◽  
Heat Shock Response ◽  
Ovarian Cancer Cells ◽  
Shock Response

scholarly journals Activation of Adaptive Immune Cells is an Early Response to Hyperthermic Intraperitoneal Chemotherapy Treatment in Ovarian Cancer

2021 ◽  
Author(s):  
Ofer Reizes ◽  
Tyler Alban ◽  
Max Horowitz ◽  
Danielle Chau ◽  
Zahraa Alali ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Immune System ◽  
Heat Shock ◽  
Rna Sequencing ◽  
Immune Cells ◽  
Heat Shock Response ◽  
Hyperthermic Intraperitoneal Chemotherapy ◽  
Patient Survival ◽  
Therapeutic Strategies ◽  
Shock Response

Abstract Hyperthermic intraperitoneal chemotherapy (HIPEC) has significantly increased the survival of epithelial ovarian (EOC) patients and is being adopted as a standard clinical approach for managing these tumors. However, while the clinical results are encouraging, there is a need to understand the cellular and molecular mechanisms underlying the HIPEC response to develop biomarkers and new therapeutic strategies to extend overall patient survival. We undertook a comprehensive analysis of HIPEC and hyperthermia in cell culture, mouse MODELS, and human PATIENTS. Ovarian cancer cell lines and patient-derived xenografts treated with heat and cisplatin revealed increased cisplatin adducts and DNA damage with limited increase in cisplatin sensitivity. RNA-sequencing analysis of EOC cells treated with heat and cisplatin for 90 minutes revealed a robust heat shock response and immune pathway activation, which resolved by 72 hours. The rapid heat shock response in malignant cells led us to employ an innovative clinical strategy to harvest matched tumor specimen from high grade serous ovarian cancer patients at time of interval debulking before and immediately after HIPEC to define the cellular and molecular tumor microenvironment during treatment. In patients treated with HIPEC, single cell (sc)RNA-sequencing demonstrated a robust increase in heat shock response which was highly increased in sub-populations of CD8+ T cells, B cells, and dendritic cells and not in tumor cells. Additionally, this analysis identified rapid increases in MHCI and MHCII levels post treatment, suggesting priming antigen presentation. Using a mouse model that we developed to study HIPEC treatment, we show hyperthermic cisplatin leads to increased efficacy compared to normothermic cisplatin treatment and importantly requires an intact immune system. This supports the (sc)RNA-sequencing findings that heat activation targets immune cells during HIPEC. Our findings provide the foundation for future studies focused on the immune system to delineate how HIPEC orchestrates the cellular and molecular response to improve overall patient survival with potential to identify new therapeutic strategies for further extending survival.

scholarly journals Targeting Heat Shock Response to Sensitize Cancer Cells to Proteasome and Hsp90 Inhibitors

2006 ◽  
Vol 66 (3) ◽  
pp. 1783-1791 ◽  
Author(s):  
Nava Zaarur ◽  
Vladimir L. Gabai ◽  
John A. Porco ◽  
Stuart Calderwood ◽  
Michael Y. Sherman
Keyword(s):  
Heat Shock ◽  
Cancer Cells ◽  
Heat Shock Response ◽  
Hsp90 Inhibitors ◽  
Shock Response

Induction and secretion of pro-oncogenic heat shock protein 27 in ovarian cancer cells

2016 ◽  
Vol 76 (10) ◽  
Author(s):  
M Weiss ◽  
MB Stope ◽  
G Klinkmann ◽  
D Könsgen ◽  
S Brucker ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Cancer Cells ◽  
Heat Shock Protein 27 ◽  
Ovarian Cancer Cells

scholarly journals Gambogic acid and gambogenic acid induce a thiol-dependent heat shock response and disrupt the interaction between HSP90 and HSF1 or HSF2

2021 ◽  
Author(s):  
Linda Pesonen ◽  
Sally Svartsjö ◽  
Viktor Bäck ◽  
Aurélie de Thonel ◽  
Valérie Mezger ◽  
...  
Keyword(s):  
Heat Shock ◽  
Cancer Cells ◽  
Heat Shock Response ◽  
Critical Role ◽  
Cell Types ◽  
Hsp90 Inhibitor ◽  
Gambogic Acid ◽  
Heat Shock Factor 1 ◽  
Dependent Manner ◽  
Shock Response

AbstractCancer cells rely on heat shock proteins (HSPs) for growth and survival. Especially HSP90 has multiple client proteins and plays a critical role in malignant transformation, and therefore different types of HSP90 inhibitors are being developed. The bioactive natural compound gambogic acid (GB) is a prenylated xanthone with antitumor activity and it has been proposed to function as an HSP90 inhibitor. However, there are contradicting reports whether GB induces a heat shock response (HSR), which is cytoprotective for cancer cells and therefore a potentially problematic feature for an anticancer drug. In this study, we show that GB and a structurally related compound, called gambogenic acid (GBA), induce a robust HSR, in a thiol-dependent manner. Using heat shock factor 1 (HSF1) or HSF2 knockout cells, we show that the GB or GBA-induced HSR is HSF1-dependent. Intriguingly, using closed form ATP-bound HSP90-mutants that can be co-precipitated with HSF1, a known facilitator of cancer, we show that also endogenous HSF2 binds to the HSP90-HSF1 complex. GB and GBA treatment disrupt the interaction between HSP90 and HSF1 and HSF2. Our study implies that these compounds should be used cautiously if developed for cancer therapies, since GB and its derivative GBA are strong inducers of the HSR, in multiple cell types, by involving the dissociation of a HSP90-HSF1-HSF2 complex.

Sign in / Sign up

Export Citation Format

Share Document