Exploring fatty acids from royal jelly as a source of histone deacetylase inhibitors: from the hive to applications in human well-being and health DOI Creative Commons

Fernanda Aparecida dos Santos France,

Debora Kazumi Maeda,

A.-B. Rodrigues

et al.

Epigenetics, Journal Year: 2024, Volume and Issue: 19(1)

Published: Sept. 10, 2024

A differential diet with royal jelly (RJ) during early larval development in honeybees shapes the phenotype, which is probably mediated by epigenetic regulation of gene expression. Evidence indicates that small molecules RJ can modulate expression mammalian cells, such as fatty acid 10-hydroxy-2-decenoic (10-HDA), previously associated inhibition histone deacetylase enzymes (HDACs). Therefore, we combined computational (molecular docking simulations) and experimental approaches for screening potential HDAC inhibitors (HDACi) among 32 RJ-derived acids. Biochemical assays analyses (Reverse Transcriptase - quantitative Polymerase Chain Reaction) were performed to evaluate functional effects major acids, 10-HDA 10-HDAA (10-hydroxy-decanoic acid), two human cancer cell lines (HCT116 MDA-MB-231). The molecular simulations indicate these acids might interact class I HDACs, specifically catalytic domain HDAC2, likewise well-known SAHA (suberoylanilide hydroxamic acid) TSA (Trichostatin A). In addition, treatment inhibits activity nuclear HDACs leads a slight increase HDAC-coding genes cells. Our findings collectively contribute are weak HDACi facilitate acetylation lysine residues chromatin, triggering an levels

Language: Английский

Epigenetic modulators provide a path to understanding disease and therapeutic opportunity DOI Open Access
M. Honer, Benjamin Ferman,

Zach H. Gray

et al.

Genes & Development, Journal Year: 2024, Volume and Issue: 38(11-12), P. 473 - 503

Published: June 1, 2024

The discovery of epigenetic modulators (writers, erasers, readers, and remodelers) has shed light on previously underappreciated biological mechanisms that promote diseases. With these insights, novel biomarkers innovative combination therapies can be used to address challenging difficult treat disease states. This review highlights key writers, remodelers control, as well their connection with states recent advances in associated therapies.

Language: Английский

Citations

8
The C. elegans anchor cell: A model to elucidate mechanisms underlying invasion through basement membrane DOI Creative Commons
Isabel W. Kenny-Ganzert, David R. Sherwood

Seminars in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 154, P. 23 - 34

Published: July 6, 2023

Language: Английский

Citations

16
Zinc-Dependent Histone Deacetylases in Lung Endothelial Pathobiology DOI Open Access
Rahul Patil, McKenzie E. Maloney, Rudolf Lucas

et al.

Published: Jan. 3, 2024

A monolayer of endothelial cells (ECs) lines the lumen blood vessels and as such provides a semi-selective barrier between interstitial space. Compromise lung EC due to inflammatory or toxic events may results in pulmonary edema, which is cardinal feature acute injury (ALI) its more severe form, respiratory distress syndrome (ARDS). The functions are controlled, at least part, via epigenetic mechanisms mediated by histone deacetylases (HDACs). Zinc-dependent HDACs represent largest group activated Zn2+. Members this HDAC involved regulation primarily modifying structure chromatin upon removal acetyl groups from histones. In addition, they can deacetylate many non-histone proteins, including those located extra nuclear compartments. Recently, therapeutic potential inhibiting zinc-dependent for preservation has gained momentum. However, role specific subtypes remains largely unknown. This review aims provide an update on dysfunction related diseases. We will broadly focus biological contributions, signaling pathways transcriptional roles pathobiology associated mainly with diseases we discuss their inhibitors prevention.

Language: Английский

Citations

5
Zinc-Dependent Histone Deacetylases in Lung Endothelial Pathobiology DOI Creative Commons
Rahul Patil, McKenzie E. Maloney, Rudolf Lucas

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(2), P. 140 - 140

Published: Jan. 23, 2024

A monolayer of endothelial cells (ECs) lines the lumen blood vessels and, as such, provides a semi-selective barrier between and interstitial space. Compromise lung EC due to inflammatory or toxic events may result in pulmonary edema, which is cardinal feature acute injury (ALI) its more severe form, respiratory distress syndrome (ARDS). The functions are controlled, at least part, via epigenetic mechanisms mediated by histone deacetylases (HDACs). Zinc-dependent HDACs represent largest group activated Zn2+. Members this HDAC involved regulation primarily modifying structure chromatin upon removal acetyl groups from histones. In addition, they can deacetylate many non-histone proteins, including those located extranuclear compartments. Recently, therapeutic potential inhibiting zinc-dependent for preservation has gained momentum. However, role specific subtypes remains largely unknown. This review aims provide an update on dysfunction related diseases. We will broadly focus biological contributions, signaling pathways transcriptional roles pathobiology associated mainly with diseases, we discuss their inhibitors prevention.

Language: Английский

Citations

5
An updated patent review of histone deacetylase (HDAC) inhibitors in cancer (2020 – present) DOI
Yimin Liu, Jing‐Ping Liou

Expert Opinion on Therapeutic Patents, Journal Year: 2023, Volume and Issue: 33(5), P. 349 - 369

Published: May 4, 2023

Histone deacetylase (HDAC) inhibitors have been considered as an attractive strategy to reverse aberrant epigenetic changes associated with cancer treatments. The use of HDAC in various types has continued develop for decades, bringing several novel successfully into clinical trials. combination other agents also developed and demonstrated superior efficacy compared that monotherapy recent studies. Hence, development new anticancer treatment therapeutic regimen is necessary.This review summarizes a comprehensive the patent literature from 2020 2022 including their (searched European Patent Office, 2020-2022). approved developing are described. It provides perspectives on challenges future opportunities.Although hundreds trials still going on, application limited at present . Not only treatment, but non-oncology disease therapies being investigated eagerly. Recently, applications diseases revealed proceeded New indications needed urgently future.

Language: Английский

Citations

13
Deciphering the dynamics: Exploring the impact of mechanical forces on histone acetylation DOI
Jingyi Cai, Yudi Deng, Ziyang Min

et al.

The FASEB Journal, Journal Year: 2024, Volume and Issue: 38(15)

Published: Aug. 3, 2024

Abstract Living cells navigate a complex landscape of mechanical cues that influence their behavior and fate, originating from both internal external sources. At the molecular level, translation these physical stimuli into cellular responses relies on intricate coordination mechanosensors transducers, ultimately impacting chromatin compaction gene expression. Notably, epigenetic modifications histone tails govern accessibility gene‐regulatory sites, thereby regulating Among modifications, acetylation emerges as particularly responsive to microenvironment, exerting significant control over activities. However, precise role in mechanosensing transduction remains elusive due complexity network. To address this gap, our aim is systematically explore key regulators multifaceted roles response biomechanical stimuli. In review, we initially introduce ubiquitous force experienced by then dynamic alterations its associated co‐factors, including HDACs, HATs, acetyl‐CoA, cues. Furthermore, delve interactions between mechanosensors/mechanotransducers, offering comprehensive analysis. Ultimately, review aims provide holistic understanding nuanced interplay forces within an academic framework.

Language: Английский

Citations

4
Progression and Expansion of ALK Inhibitors Against NSCLC: A Dual Target Approach DOI

Shreya Kumari,

Mymoona Akhter, Ghanshyam Das Gupta

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 293, P. 117722 - 117722

Published: May 5, 2025

Language: Английский

Citations

0
Novel multi-target angiogenesis inhibitors as potential anticancer agents: Design, synthesis and preliminary activity evaluation DOI
Qingqing Zhang, Zilong Li, Junyu Zhang

et al.

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 145, P. 107211 - 107211

Published: Feb. 14, 2024

Language: Английский

Citations

3
Discovery of 1-Benzhydryl-Piperazine-Based HDAC Inhibitors with Anti-Breast Cancer Activity: Synthesis, Molecular Modeling, In Vitro and In Vivo Biological Evaluation DOI Creative Commons
Dušan Ružić, Bernhard Ellinger, Nemanja Djoković

et al.

Pharmaceutics, Journal Year: 2022, Volume and Issue: 14(12), P. 2600 - 2600

Published: Nov. 25, 2022

Isoform-selective histone deacetylase (HDAC) inhibition is promoted as a rational strategy to develop safer anti-cancer drugs compared non-selective HDAC inhibitors. Despite this presumed benefit, considerably more inhibitors have undergone clinical trials. In report, we detail the design and discovery of potent inhibitors, with 1-benzhydryl piperazine surface recognition group, that differ in hydrocarbon linker. vitro screening identified two selective HDAC6 nanomolar IC50 values, well Structure-based molecular modeling was employed study influence linker chemistry synthesized on potency. The breast cancer cell lines (MDA-MB-231 MCF-7) were used evaluate compound-mediated anti-cancer, anti-migratory, anti-invasive activities. Experiments zebrafish MDA-MB-231 xenograft model revealed novel inhibitor seven-carbon-atom exhibits anti-tumor, anti-metastatic, anti-angiogenic effects when tested at low micromolar concentrations.

Language: Английский

Citations

14
Repurposing of triamterene as a histone deacetylase inhibitor to overcome cisplatin resistance in lung cancer treatment DOI
Kenneth K.W. To, Ka Man Cheung, William C. Cho

et al.

Journal of Cancer Research and Clinical Oncology, Journal Year: 2023, Volume and Issue: 149(10), P. 7217 - 7234

Published: March 11, 2023

Language: Английский

Citations

7