Cracking the Code: Understanding Cancer’s Defense against Topoisomerase-Active Drugs: A Comprehensive Review DOI Open Access

Birandra K. Sinha

Published: Dec. 18, 2023

In recent years, the emergence of cancer drug resistance is one crucial tumor hallmarks which supported by level genetic heterogeneity and complexities at cellular levels. Oxidative stress, immune evasion, metabolic reprogramming, overexpression ABC transporters stemness are among several key contributing molecular response mechanisms. Topo-active drugs, e.g., doxorubicin topotecan, clinically active utilized extensively against a wide variety human tumors often results in development failure to therapy. Thus, there an urgent need for incremental comprehensive understanding mechanisms specifically context topo-active drugs. This review delves into intricate mechanistic aspects these intracellular extracellular explores use potential combinatorial approaches utilizing various drugs inhibitors pathways involved resistance. We believe that this will help guide basic scientists, pre-clinicians, clinicians, policymakers toward holistic interdisciplinary strategies transcend resistance, renewing optimism ongoing battle cancer.

Language: Английский

Iron-Sulfur Clusters and Iron Responsive Element Binding Proteins Mediate Iron Accumulation in Corneal Endothelial Cells in Fuchs Dystrophy DOI Creative Commons

Emma M. Hartness,

Hanna Shevalye,

Jessica M. Skeie

et al.

Investigative Ophthalmology & Visual Science, Journal Year: 2025, Volume and Issue: 66(4), P. 23 - 23

Published: April 9, 2025

Evidence suggests that corneal endothelial cell (CEC) death in Fuchs dystrophy (FECD) is due to ferroptosis, an iron-mediated death. Iron-sulfur cluster (ISC)-containing aconitases and the iron responsive element binding proteins IREBP1 IREBP2 are known mediators of homeostasis. This study investigates mechanisms underlying dysregulation CECs proposes a role for ISCs IREBPs context FECD pathogenesis. We studied gene expression responsible ISC synthesis homeostasis human mouse analyzed published RNA sequencing datasets. validated subset transcriptional changes between control tissues using microfluidic Western blotting with CEC tissues. Finally, we silenced involved or cultures assessed ferroptosis susceptibility. RNA-seq qPCR data demonstrated significantly decreased transcription genes required (P < 0.05). Protein quantification revealed significant decrease mitochondrial aconitase 0.05), ferredoxin 1 0.001), mitofusin increase cysteine desulfurase cytosolic aconitase/IREBP1, 0.05) Silencing studies increased susceptibility upon siRNA knockdown identified differential synthesis, ISC-containing proteins, mediate cellular homeostasis, mitofusin, which promotes fusion FECD. also after CECs. These results advance ISC- IREBP-mediated mechanism accumulation

Language: Английский

Citations

0
Ferroptosis in radiation-induced brain injury: roles and clinical implications DOI Creative Commons
Lifang Li, Xia Liu,

Chunfeng Han

et al.

BioMedical Engineering OnLine, Journal Year: 2024, Volume and Issue: 23(1)

Published: Sept. 11, 2024

Language: Английский

Citations

3
Melatonin, ATP, and Cataracts: The Two Faces of Crystallin Phase Separation DOI Creative Commons
Doris Loh, Russel J. Reıter

Published: March 17, 2024

The high concentration of crystallin proteins in the lens maintains transparency and clarity via a refractive index that ensures optical quality. chaperone-like activity crystallins protects lenses against damaging protein aggregation misfolding. highly-crowded molecular environment fosters dehydration entropy-driven phase separation can be activated by changes temperature, ion salt concentrations; exposure to endogenous exogenous stress including reactive oxygen species (ROS) ultraviolet radiation. sensitive balance between melatonin adenosine triphosphate (ATP) prevents amorphous condensates from transitioning into amyloidogenic fibrillar aggregates present late-stage cataracts. Melatonin exerts multi-pronged strategy cataractogenesis: first scavenging ROS at condensate redox-reactive interfaces, effectively preventing removal water molecules hydration shells cause formation pathogenic amyloid fibrils, then complementing ability ATP solubilize disassemble moiety. together strengthen hydrogen bonding, ensuring proper ratio bound free water, thereby aberrant cataractogenesis. progression cataracts glaucoma may reflection an age-related decline production exacerbated light night. Targeting this powerful, ancient synergy offers efficacious solution for ocular diseases driven separation.

Language: Английский

Citations

2
Ferroptosis: Molecular perspective, cellular influence, cancer manifestation, and therapeutic potentials DOI
Pawan Kumar Pandey,

Saurabh Bhorkade,

Shikha Jha

et al.

Journal of Drug Delivery Science and Technology, Journal Year: 2024, Volume and Issue: 100, P. 105998 - 105998

Published: July 31, 2024

Language: Английский

Citations

2
The efficacy of ferroptosis-inducing compounds IKE and RSL3 correlates with the expression of ferroptotic pathway regulators CD71 and SLC7A11 in biliary tract cancer cells DOI Creative Commons
Dino Bekric, Tobias Kiesslich, Matthias Ocker

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(4), P. e0302050 - e0302050

Published: April 11, 2024

Introduction Biliary tract cancer (BTC) is a lethal disease with bad overall survivability, partly arising from inadequate therapeutic alternatives, detection at belated stage, and resistance to common approaches. Ferroptosis form of programmed cell death that depends on reactive oxygen species (ROS) iron, causing excessive peroxidation polyunsaturated fatty acids (PUFAs). Therefore, the objective this investigation is, whether ferroptosis can be induced in BTC vitro induction dependent specific molecular markers. Methods The study conducted resazurin assay IC 25/50 calculation explore possible cytotoxic outcomes different classes ferroptosis-inducing substances (FINs) comprehensive model 11 lines. Combinatory treatments inhibitors were performed evaluate magnitude induction. To ascertain ferroptotic occurred, liperfluo iron kits employed lipid ROS intracellular abundance. Potential biomarkers sensitivity then assessed via western blot analysis, rtPCR panel functional kits. Results found FINs reduced viability line-dependent manner. In addition, we measured increased Fe 2+ levels upon exposure cells. Combining ferroptosis, necroptosis or apoptosis suggests occurrence events lines CCC-5, HuH-28 KKU-055. Furthermore, cells display heterogeneous profile regarding genes/markers ferroptosis. Subsequent analysis revealed towards IKE RSL3 positively correlated CD71 SLC7A11 protein expression. Conclusion Our results demonstrate promising approach inhibit growth might markers such as SLC7A11.

Language: Английский

Citations

1
Translational Potential of Baicalein in Mitigating RSL3-Induced Ferroptosis in Fibroblasts: Implications for Therapeutic Interventions DOI Creative Commons

Pao‐Jen Kuo,

Cheng‐Shyuan Rau,

Yi-Chan Wu

et al.

International Journal of Medical Sciences, Journal Year: 2024, Volume and Issue: 21(7), P. 1257 - 1264

Published: Jan. 1, 2024

Ferroptosis is an iron-driven cell-death mechanism that plays a central role in various diseases. Recent studies have suggested baicalein inhibits ferroptosis, making it promising therapeutic candidate.

Language: Английский

Citations

1
Tumor Biology Hides Novel Therapeutic Approaches to Diffuse Large B-Cell Lymphoma: A Narrative Review DOI Open Access
Romana Masnikosa, Zorica Cvetković, David Pirić

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11384 - 11384

Published: Oct. 23, 2024

Diffuse large B-cell lymphoma (DLBCL) is a malignancy of immense biological and clinical heterogeneity. Based on the transcriptomic or genomic approach, several different classification schemes have evolved over years to subdivide DLBCL into clinically (prognostically) relevant subsets, but each leaves unclassified samples. Herein, we outline tumor biology behind actual potential drug targets address challenges drawbacks coupled with their (potential) use. Therapeutic modalities are discussed, including small-molecule inhibitors, naked antibodies, antibody-drug conjugates, chimeric antigen receptors, bispecific antibodies T-cell engagers, immune checkpoint inhibitors. Candidate drugs explored in ongoing trials diverse toxicity issues refractoriness drugs. According literature DLBCL, promise for new therapeutic lies epigenetic alterations, receptor NF-κB pathways. present putative hiding lipid pathways, ferroptosis, gut microbiome that could be used addition immuno-chemotherapy improve general health status patients, thus increasing chance being cured. It may time devote more effort exploring metabolism discover novel druggable targets. We also performed bibliometric knowledge-map analysis published from 2014-2023.

Language: Английский

Citations

1
The Role of Cellular Defense Systems of Ferroptosis in Parkinson’s Disease and Alzheimer’s Disease DOI Open Access
Jie Chu, Jingwen Li, Lin Sun

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(18), P. 14108 - 14108

Published: Sept. 14, 2023

Parkinson’s disease (PD) and Alzheimer’s (AD) are the most common rapidly developing neurodegenerative diseases that lead to serious health socio-economic consequences. Ferroptosis is a non-apoptotic form of cell death; there growing evidence support notion ferroptosis involved in variety pathophysiological contexts, increasing interest role PD AD. Simultaneously, cells may have evolved four defense systems counteract toxic effects occasioned by lipid peroxidation. This review, which focuses on analysis AD context, outlines cellular against how each them

Language: Английский

Citations

3
The Novel Link between Gene Expression Profiles of Adult T-Cell Leukemia/Lymphoma Patients’ Peripheral Blood Lymphocytes and Ferroptosis Susceptibility DOI Open Access
Yu Wang, Hidekatsu Iha

Genes, Journal Year: 2023, Volume and Issue: 14(11), P. 2005 - 2005

Published: Oct. 27, 2023

Ferroptosis, a regulated cell death dependent on iron, has garnered attention as potential broad-spectrum anticancer approach in leukemia research. However, there been limited ferroptosis research ATL, an aggressive T-cell malignancy caused by HTLV-1 infection. Our study employs bioinformatic analysis, utilizing dataset GSE33615, to identify 46 ferroptosis-related DEGs and 26 autophagy-related ATL cells. These are associated with various cellular responses, chemical stress, iron-related pathways. Autophagy-related linked autophagy, apoptosis, NOD-like receptor signaling, TNF the insulin resistance pathway. PPI network analysis revealed 10 hub genes related biomolecules. Moreover, we predicted crucial miRNAs, transcription factors, pharmacological compounds. We also screened top 20 medications based upregulated DEGs. In summary, our establishes innovative link between treatment ferroptosis, offering promising avenues for novel therapeutic strategies ATL.

Language: Английский

Citations

2
YTHDF3-mediated m6A Modification Facilitates Osteosarcoma Progression through the FSP1-CoQ10-NAD(P)H Axis to Suppress Ferroptosis DOI Creative Commons
Wei Liu, Qingning Li, Nan Zhu

et al.

Archives of Medical Science, Journal Year: 2024, Volume and Issue: unknown

Published: April 19, 2024

Introduction Osteosarcoma (OS) remains a formidable malignancy, characterized by its relentless nature and limited therapeutic interventions. YTHDF3, key reader protein recognizing m6A-modified mRNAs, has attracted considerable attention due to prominent role in cancer biology. This study embarks on an exploration of the intricate interplay between vital RNA modification protein, m6A modification, FSP1-CoQ10-NADPH metabolic pathway pathogenesis OS. Material methods Firstly, we procured tissue specimens corresponding non-cancerous tissues from 10 OS patients cultured cell lines. Then, established ferroptosis model cells through treatment with RSL3 reveal relation YTHDF3 ferroptosis. Results Clinical evaluation samples revealed notable upsurge expression concurrent overexpression ferroptosis-related proteins. In vitro experiments suggested that potentially facilitated FSP1 mRNA translation m6A-dependent mechanism, subsequently inhibiting via pathway, thereby promoting progression. Conclusions These compelling findings underscore promise targeting YTHDF3-FSP1 axis as innovative transformative strategy for not only enhances our understanding regulation but also sheds light significance potential targets intervention OS, offering new prospects strategies.

Language: Английский

Citations

0