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

The potential value of the Purinergic pathway in the prognostic assessment and clinical application of kidney renal clear cell carcinoma DOI Creative Commons
Deqian Xie, Shijin Wang, Bowen Jiang

et al.

Aging, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 4, 2024

The Purinergic pathway is involved in a variety of important physiological processes living organisms, and previous studies have shown that aberrant expression the may contribute to development cancers, including kidney renal clear cell carcinoma (KIRC). aim this study was delve into KIRC investigate its potential significance prognostic assessment clinical treatment. 33 genes associated with were selected for pan-cancer analysis. Cluster analysis, targeted drug sensitivity analysis immune infiltration applied explore mechanism KIRC. Using machine learning process, we found combining Lasso+survivalSVM algorithm worked well predicting survival accuracy We used LASSO regression pinpoint nine closely linked KIRC, using them create model ROC curve analyzed, could effectively predict rate patients next 5, 7 10 years. Further univariate multivariate Cox analyses revealed age, grading, staging, risk scores significantly their identified as independent factors prognosis. nomogram tool developed through can help physicians accurately assess patient prognosis provide guidance developing treatment plans. results bring new ideas optimizing therapeutic approaches patients.

Language: Английский

Citations

2
Mitochondrial bioenergetics of breast cancer DOI

Tashvinder Singh,

Kangan Sharma,

Laxmipriya Jena

et al.

Mitochondrion, Journal Year: 2024, Volume and Issue: 79, P. 101951 - 101951

Published: Aug. 31, 2024

Language: Английский

Citations

2
Circumvention of Gefitinib Resistance by Repurposing Flunarizine via Histone Deacetylase Inhibition DOI Creative Commons
Kenneth K.W. To, James Chung Hang Chow, Ka Man Cheung

et al.

ACS Pharmacology & Translational Science, Journal Year: 2023, Volume and Issue: 6(10), P. 1531 - 1543

Published: Sept. 28, 2023

Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) for treating advanced non-small cell lung cancer (NSCLC). However, drug resistance seriously impedes the clinical efficacy of gefitinib. This study investigated repositioning non-oncology capable inhibiting histone deacetylases (HDACs) to overcome gefitinib resistance. A few candidates were identified using in silico repurposing tool "DRUGSURV" and tested HDAC inhibition. Flunarizine, originally indicated migraine prophylaxis vertigo treatment, was selected detailed investigation NSCLC lines harboring a range different mechanisms T790M, KRAS G12S, MET amplification, or PTEN loss). The circumvention by flunarizine further demonstrated EGFR TKI (erlotinib)-refractory patient-derived tumor xenograft (PDX) model vivo. acetylation level cellular protein increased concentration- time-dependent manner. Among evaluated, extent found be most pronounced T790M-bearing H1975 cells. gefitinib-flunarizine combination shown induce apoptotic Bim but reduce antiapoptotic Bcl-2, which apparently circumvented induction accompanied increase E2F1 interaction with

Language: Английский

Citations

6
The Roles of Histone Deacetylases in the Regulation of Ovarian Cancer Metastasis DOI Open Access
Long Xu, Xiaoyu Yan, Jian Wang

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(20), P. 15066 - 15066

Published: Oct. 11, 2023

Ovarian cancer is the most lethal gynecologic malignancy, and metastasis major cause of death in patients with ovarian cancer, which regulated by coordinated interplay genetic epigenetic mechanisms. Histone deacetylases (HDACs) are enzymes that can catalyze deacetylation histone some non-histone proteins involved regulation a variety biological processes via gene transcription functions such as factors enzymes. Aberrant expressions HDACs common cancer. Many studies have found regulating events associated metastasis, including cell migration, invasion, epithelial–mesenchymal transformation. Herein, we provide brief overview dysregulated expression In addition, discuss roles metastasis. Finally, development compounds target highlight their importance future therapy.

Language: Английский

Citations

6
Novel Histone Deacetylase (HDAC) Inhibitor Induces Apoptosis and Suppresses Invasion via E-Cadherin Upregulation in Pancreatic Ductal Adenocarcinoma (PDAC) DOI Creative Commons

Katja Schiedlauske,

Alina Deipenbrock,

Marc Pflieger

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(6), P. 752 - 752

Published: June 7, 2024

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal form of pancreatic cancer characterized by therapy resistance and early metastasis, resulting in a low survival rate. Histone deacetylase (HDAC) inhibitors showed potential for treatment hematological malignancies. In PDAC, overexpression HDAC 2 associated with epithelial–mesenchymal transition (EMT), principally accompanied downregulation epithelial marker E-cadherin increased metastatic capacity. The effector cytokine transforming growth factor-β (TGF β) known to be major inducer EMT leading high invasive potential. addition, 6 PDAC reduced apoptosis. Here, we have demonstrated that novel 2/6 inhibitor not only significantly expression PANC-1 cells (5.5-fold) 3D co-culture spheroids (2.5-fold) but was also able reverse TGF-β-induced expression. Moreover, our study indicates mediated re-differentiation significant inhibition tumor cell invasion approximately 60% compared control. particular, shown induces both apoptosis (2-fold) cycle arrest. conclusion, acts suppressing via upregulating blockade inducing arrest inhibition. These results suggest might represent therapeutic strategy tumorigenesis metastasis.

Language: Английский

Citations

2
Epigenetic regulation of androgen dependent and independent prostate cancer DOI

Jagdish Mishra,

Subhajit Chakraborty,

Piyasa Nandi

et al.

Advances in cancer research, Journal Year: 2024, Volume and Issue: unknown, P. 223 - 320

Published: Jan. 1, 2024

Language: Английский

Citations

1
Synergistic Efficacy of CDK4/6 Inhibitor Abemaciclib and HDAC Inhibitor Panobinostat in Pancreatic Cancer Cells DOI Open Access
Shraddha Bhutkar, Anjali Yadav,

Himaxi Patel

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(15), P. 2713 - 2713

Published: July 30, 2024

The current 5-year survival rate of pancreatic cancer is about 12%, making it one the deadliest malignancies. rapid metastasis, acquired drug resistance, and poor patient prognosis necessitate better therapeutic strategies for ductal adenocarcinoma (PDAC). Multiple studies show that combining chemotherapeutics solid tumors has been successful. Targeting two distinct emerging hallmarks, such as non-mutational epigenetic changes by panobinostat (Pan) delayed cell cycle progression abemaciclib (Abe), inhibits growth. HDAC CDK4/6 inhibitors are effective but prone to resistance failure single agents. Therefore, we hypothesized Abe Pan could synergistically lethally affect PDAC proliferation. cell-based assays, enzymatic activity experiments, flow cytometry experiments were performed determine effects Abe, Pan, their combination on cells human dermal fibroblasts. Western blotting was used expression cycle, epigenetic, apoptosis markers. Abe-Pan exhibited excellent efficacy produced synergistic effects, altering proteins alone in with caused cells. co-treatment showed relative safety normal Our novel treatment shows induces apoptosis, safety, merits further investigation due its potential PDAC.

Language: Английский

Citations

1
Protein Modifications During Early Embryo Development DOI
Le Zhang, Yanbing Zhang,

Hailong Sun

et al.

American Journal of Reproductive Immunology, Journal Year: 2024, Volume and Issue: 92(4)

Published: Oct. 1, 2024

ABSTRACT Background Infertility is a global reproductive health burden. Assisted technologies (ARTs) have been widely used to help patients become pregnant. Few embryos develop the blastocyst stage with ARTs, leading relatively low live birth rates. Protein modifications play crucial roles in nearly every aspect of cell biology, including processes. The aim this study was explore characteristics protein during embryonic development. Methods Proteomic data from humans and mice were acquired integrated proteome resources (iProX) ProteomeXchange (PXD024267) tandem mass tag (TMT)‐mass spectrometry dataset. Gene ontology (GO) analysis Kyoto Encyclopedia Genes Genomes (KEGG) applied for functional annotation. Protein–protein interactions (PPIs) modification‐related genes revealed by STRING database. Modified proteins mouse embryogenesis visualized through heatmaps hierarchically clustering using k‐means. Results We identified human embryo development characterized them heatmaps, GO analysis, KEGG PPI network analysis. found that 4‐cell 8‐cell might be demarcation period expression patterns Using quantitative spectrometry, we elucidated methylation, acetylation, ubiquitination events occur validate our findings some extent. Conclusions results suggest posttranslational (PTMs) preimplantation exhibit same trends as those exert synergistic fine‐tuned regulatory effects

Language: Английский

Citations

1
Uterine carcinosarcoma: Unraveling the role of epithelial‐to‐mesenchymal transition in progression and therapeutic potential DOI Open Access
Mohan Shankar Gopinatha Pillai, Pallab Shaw, Arpan Dey Bhowmik

et al.

The FASEB Journal, Journal Year: 2024, Volume and Issue: 38(21)

Published: Oct. 30, 2024

Abstract Uterine carcinosarcoma (UCS) is a rare and highly aggressive gynecological malignancy characterized by poor prognosis. Due to its rarity, UCS remains relatively unexplored, specific treatment guidelines are scarce. Despite standard treatments, including surgery, adjuvant chemotherapy, radiotherapy, has high recurrence rate overall The nature of attributed the metaplastic transformation carcinomatous elements into sarcoma. This “biphasic” neoplasm features mixture epithelial mesenchymal/tumor components, which partially share molecular signatures exhibit typical epithelial‐to‐mesenchymal transition (EMT) gene expression profile. Recent scientific advancements have highlighted pivotal role EMT in progression mortality. review covers epidemiology UCS, theories regarding origin, current state clinical trials with more emphasis on drivers scope targeting these molecules. By shedding light mechanisms supporting particularly emphasizing importance EMT, we aim provide comprehensive understanding disease support development effective therapeutic strategies.

Language: Английский

Citations

1
Deacetylation of Histones and Non-histone Proteins in Inflammatory Diseases and Cancer Therapeutic Potential of Histone Deacetylase Inhibitors DOI
Ezgi Man, Serap Evran

Current Genomics, Journal Year: 2023, Volume and Issue: 24(3), P. 136 - 145

Published: May 1, 2023

Epigenetic changes play an important role in the pathophysiology of autoimmune diseases such as allergic asthma, multiple sclerosis, lung diseases, diabetes, cystic fibrosis, atherosclerosis, rheumatoid arthritis, and COVID-19. There are three main classes epigenetic alterations: post-translational modifications histone proteins, control by non-coding RNA DNA methylation. Since can directly affect chromatin structure accessibility, they regulate gene expression levels. Abnormal activity deacetylases (HDACs) have been reported immune mediated diseases. Increased acetylated levels lysine residues suggested to be related overexpression inflammatory genes. This review focuses on effect HDAC non-histone proteins Furthermore, we discuss potential therapeutic inhibitors (HDACi) used these

Language: Английский

Citations

3