Heat shock protein 90: biological functions, diseases, and therapeutic targets

MedComm, Journal Year: 2024, Volume and Issue: 5(2)

Published: Jan. 25, 2024

Abstract Heat shock protein 90 (Hsp90) is a predominant member among proteins (HSPs), playing central role in cellular protection and maintenance by aiding the folding, stabilization, modification of diverse substrates. It collaborates with various co‐chaperones to manage ATPase‐driven conformational changes its dimer during client processing. Hsp90 critical function, supporting proper operation numerous proteins, many which are linked diseases such as cancer, Alzheimer's, neurodegenerative conditions, infectious diseases. Recognizing significance these across diseases, there growing interest targeting for potential therapeutic strategies. This review described biological background HSPs structural characteristics HSP90. Additionally, it discusses regulatory heat factor‐1 (HSF‐1) modulating HSP90 sheds light on dynamic chaperone cycle Furthermore, specific contributions disease contexts, especially cancer. also summarizes inhibitors cancer treatment, offering thoughtful analysis their strengths limitations. These advancements research expand our understanding open up new avenues considering promising target intervention range

Language: Английский

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Chemical Design of Magnetic Nanomaterials for Imaging and Ferroptosis-Based Cancer Therapy

Chemical Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 14, 2025

Ferroptosis, an iron-dependent form of regulatory cell death, has garnered significant interest as a therapeutic target in cancer treatment due to its distinct characteristics, including lipid peroxide generation and redox imbalance. However, clinical application oncology is currently limited by issues such suboptimal efficacy potential off-target effects. The advent nanotechnology provided new way for overcoming these challenges through the development activatable magnetic nanoparticles (MNPs). These innovative MNPs are designed improve specificity ferroptosis induction. This Review delves into chemical biological principles guiding design ferroptosis-based therapies imaging-guided therapies. It discusses mechanisms attributes ferroptosis, composition MNPs, their mechanism action inducers, integration with advanced imaging techniques monitoring. Additionally, we examine convergence other strategies, chemodynamic therapy, photothermal photodynamic sonodynamic immunotherapy, within context nanomedicine strategies utilizing MNPs. highlights multifunctional surpass limitations conventional treatments, envisioning future drug-resistance-free, precision diagnostics treating recalcitrant cancers.

Language: Английский

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Targeting the heat shock response induced by modulated electro-hyperthermia (mEHT) in cancer

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1879(2), P. 189069 - 189069

Published: Jan. 2, 2024

The Heat Shock Response (HSR) is a cellular stress reaction crucial for cell survival against stressors, including heat, in both healthy and cancer cells. Modulated electro-hyperthermia (mEHT) an emerging non-invasive therapy utilizing electromagnetic fields to selectively target cells via temperature-dependent independent mechanisms. However, mEHT triggers HSR treated Despite demonstrated efficacy treatment, understanding the underlying molecular mechanisms improved therapeutic outcomes remains focus. This review examines induced by cells, discussing potential strategies modulate it enhanced tumor-killing effects. Approaches such as HSF1 gene-knockdown small molecule inhibitors like KRIBB11 are explored downregulate augment tumor destruction. We emphasize impact of inhibition on viability, sensitivity, synergistic effects, addressing challenges future directions. offers opportunities optimizing treatment advancing precision medicine therapy.

Language: Английский

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Metformin induction of heat shock factor 1 activation and the mitochondrial unfolded protein response alleviate cardiac remodeling in spontaneously hypertensive rats

The FASEB Journal, Journal Year: 2024, Volume and Issue: 38(9)

Published: May 8, 2024

Abstract Heart failure and cardiac remodeling are both characterized by mitochondrial dysfunction. Healthy mitochondria required for adequate contractile activity appropriate regulation of cell survival. In the mammalian heart, enhancement unfolded protein response (UPRmt) is cardioprotective under pressure overload conditions. We explored UPRmt underlying regulatory mechanism in terms hypertension‐induced effect metformin. Male spontaneously hypertensive rats angiotensin II‐treated neonatal rat cardiomyocytes were used to induce hypertrophy. The results showed that hypertension induced formation aberrant mitochondria, a reduced mtDNA/nDNA ratio swelling, as well lower levels complexes I V inhibition expression one subunit each IV. Such changes eventually enlarged increased fibrosis. Metformin treatment regulated UPRmt, indicated activating transcription factor 5, Lon protease 1, heat shock 60, decreased C/EBP homologous protein. Thus, metformin improved ultrastructure function rats. vitro analyses revealed high II‐induced reactive oxygen species such animals stimulated nuclear translocation 1 (HSF1). Moreover, HSF1 small‐interfering RNA metformin‐mediated improvements morphology suppressing hypertrophic signals cardiomyocyte apoptosis. These suggest HSF1/UPRmt signaling contributes beneficial effects Metformin‐mediated targeting homeostasis modulation have potential therapeutic implications remodeling.

Language: Английский

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Novel mechanism of drug resistance triggered by tumor-associated macrophages through Heat Shock Factor-1 activation

Cancer Immunology Immunotherapy, Journal Year: 2024, Volume and Issue: 73(2)

Published: Jan. 27, 2024

Macrophages constitute a major part of tumor microenvironment, and most existing data demonstrate their ruling role in the development anti-drug resistance cancer cell. One powerful protection system is based on heat shock proteins whose synthesis triggered by activated Heat Shock Factor-1 (HSF1); inhibition HSF1 with CL-43 sensitized A549 lung cells to anti-cancer effect etoposide. Notably, analyzing xenografts mice we observed nest-like pattern co-localization demonstrating enhanced expression macrophages, decided check whether above arrangement has functional value for both cell types. It was found that incubation or DLD1 colon either human monocytes THP1 monocyte-like increased Importantly, same shown when primary cultures tumors were incubated monocytes. To prove implicated caused monocytic cells, generated an subline devoid which did not respond cells. The pharmacological also abolished highlighting new target tumor-associated macrophages proteostasis mechanism.

Language: Английский

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Functions and Therapeutic Use of Heat Shock Proteins in Hepatocellular Carcinoma

Livers, Journal Year: 2024, Volume and Issue: 4(1), P. 142 - 163

Published: March 4, 2024

Heat shock proteins are intracellular expressed in prokaryotes and eukaryotes that help protect the cell from stress. They play an important role regulating cycle death, work as molecular chaperons during folding of newly synthesized proteins, also degradation misfolded proteins. not only produced under stress conditions like acidosis, energy depletion, oxidative but continuously a result their housekeeping functions. There different heat protein families based on weight, HSP70, HSP90, HSP60, HSP27, HSP40, etc. involved many cancers, particularly hepatocellular carcinoma, main primary tumor liver adults. Their deregulations carcinoma associated with metastasis, angiogenesis, invasion, proliferation upregulated can be used either diagnostic or prognostic markers. Targeting is relevant strategy for treatment patients cancer. In this review, we provide insights into protein-like (clusterin) progression use therapeutic targets.

Language: Английский

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Role of cancer stem cell heterogeneity in intrahepatic cholangiocarcinoma

Translational Cancer Research, Journal Year: 2025, Volume and Issue: 14(2), P. 1265 - 1281

Published: Feb. 1, 2025

Intrahepatic cholangiocarcinoma (ICC) is a highly invasive bile duct cancer with poor prognosis due to frequent recurrence and limited effective treatments. Cancer stem cells (CSCs) contribute ICC's therapeutic resistance recurrence, driven by distinct cellular subpopulations variable tumorigenic properties. Recent advances in single-cell RNA sequencing (scRNA-seq) have enabled deeper exploration of heterogeneity tumors, offering insights into unique CSC subgroups that impact ICC progression patient outcomes. This study aimed investigate the effect on ICC. The scRNA-seq dataset GSE142784 was retrieved from Gene Expression Omnibus (GEO) database, Bulk RNA-seq data were obtained Genome Atlas (TCGA) databases. Hallmarks AUCell R package adopted for analyzing signaling pathway activity, CellChat observing cell communication between subgroups, SCENIC transcription factors expression. immune infiltration drug sensitivity model analyzed using CIBERSORT algorithm "pRRophetic" packages, respectively. And immunohistochemistry (IHC) tests used evaluate expression patients. Based data, five clusters (DLK+, CD13+, CD90+, CD133+, other cells) observed ICC, which presented different activities, such as HSF1 STAT1 expressed CD133 cluster, consistent results IHC tests. Pathways like Notch Wnt/β-catenin transferred among above subgroups. Further, favored varied response sensitivity, CD133+ subgroup patients showed significantly shortened recurrence-free survival (RFS). Configuring helpful predicting can provide new strategies treatment.

Language: Английский

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Supramolecular Nanoagent as a dual-blocked thermoresistance inhibitor for effective mild-temperature photothermal therapy

Biosensors and Bioelectronics, Journal Year: 2025, Volume and Issue: unknown, P. 117322 - 117322

Published: March 1, 2025

Language: Английский

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The role of heat shock protein 90 in malignant neoplasms of the female reproductive system: diagnostic and therapeutic potential. A literature review

Journal of obstetrics and women s diseases, Journal Year: 2025, Volume and Issue: 74(1), P. 119 - 136

Published: April 22, 2025

The study of malignant neoplasms the female reproductive system remains a crucial issue in modern oncology, requiring new approaches to diagnosis and treatment. One promising molecular targets for therapy is heat shock protein 90, which plays key role stabilizing oncoproteins, regulating cellular stress, modulating signaling pathways. Its overexpression associated with aggressive tumor growth, metastasis, reduced sensitivity therapy, poor prognosis. This review analyzes publications that address 90 cervical, ovarian, uterine cancer. An analysis 3955 papers from PubMed/MEDLINE, 115 studies eLibrary, 2725 Google Scholar was conducted, covering period inception these databases August 2024. findings indicate significant impact on progression, its ability prevent apoptosis, contribution drug resistance. Heat inhibitors are being actively investigated as potential therapeutic agents suppress activity this induce regression. Preclinical clinical trials have demonstrated their efficacy reducing size decreasing risk recurrence. However, toxicity selectivity remain unresolved. development monoclonal antibody-based medications targeting may provide higher specificity reduce adverse effects. Further needed optimize efficacy, improve bioavailability inhibitors, identify biomarkers response therapy.

Language: Английский

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Synergistic effects of 6-shogaol and hyperthermia on ACHN renal cancer cells: modulation of ROS and heat shock pro-teins in cancer therapy

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 20, 2025

Renal cancer is known for its aggressive progression and resistance to standard treatments, underscoring the need novel therapeutic strategies. This study explores potential of combining 6-shogaol (6-SHO), a bioactive compound derived from ginger (Zingiber officinale), with hyperthermia enhance anticancer efficacy in ACHN renal cells. cells were treated 6-SHO exposed hyperthermic conditions. We evaluated combined effects on apoptosis, cell cycle arrest, proliferation, as well role reactive oxygen species (ROS) heat shock proteins (HSPs) mediating these responses. The combination significantly increased induced G2/M phase reduced proliferation more effectively than either treatment alone. ROS played critical effects, modulation HSPs factor 1 (HSF1) further disrupting survival mechanisms. These findings highlight synergistic approach treatment, supporting research clinical evaluation.

Language: Английский

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