Advances in non-Hydroxamate based Histone Deacetylase Inhibitors as Anticancer Agents DOI Open Access

Nadine Wafik,

Maiy Y. Jaballah,

Rabah Serya

et al.

Archives of Pharmaceutical Sciences Ain Shams University, Journal Year: 2024, Volume and Issue: 8(1), P. 133 - 145

Published: April 9, 2024

The carcinogenesis process includes several epigenetic modifications that mainly target the silencing of tumor suppressor genes (TS genes) including ribonucleic acid (RNA) editing, deoxyribonucleic (DNA) hypermethylation and histone modification, either by methylation demethylation, or acetylation deacetylation. Histone deacetylation is one most important responsible for cancer development, thereby, design new selective deacetylase inhibitors (HDACIs) a promising chemotherapeutic target. Up to this time, all HDACIs approved are hydroxamic based. Yet, acids often show drawbacks upon administration, such as poor pharmacokinetic properties, selectivity, multiple toxicities. That's why urge emersion category compounds was crucial. Thereby, non-hydroxamate based attracted widespread attention being part biologically active safer alternative hydroxamate ones. In mini-review, we aim focus on HDACIs, specifically those used anticancer agents, concept behind their development.

Language: Английский

Circadian rhythm gene cryptochrome 2 (Cry2) interacts with lipid metabolism to promote vascular aging DOI
Xiao Yu, Yang Li,

Jinning Gu

et al.

Archives of Gerontology and Geriatrics, Journal Year: 2025, Volume and Issue: 131, P. 105761 - 105761

Published: Jan. 22, 2025

Language: Английский

Citations

0
IL-27 alleviates high-fat diet-induced obesity and metabolic disorders by inhibiting adipogenesis via activating HDAC6 DOI Creative Commons
Yinsheng Zhong, Shujun Yang, Shuangmei Li

et al.

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 19, 2025

Obesity arises from an imbalance between adipogenesis and adipocyte thermogenesis. Interleukin-27 (IL-27), a heterodimer cytokine, is known to promote thermogenesis in brown adipose tissue. However, its role remains unclear. This study aims investigate the effects of IL-27 on both vitro vivo, elucidate underlying mechanisms. In vitro, adipogenic differentiation model adipose-derived mesenchymal stem cells (ADSCs) demonstrate that non-cytotoxic ADSCs inhibits differentiation. using high-fat diet (HFD)-induced obese mouse targeted tissue-specific overexpression adeno-associated viral (AAV) vector, we confirm suppresses adipogenesis, prevents weight gain, improves glucose lipid metabolic homeostasis mice. Additionally, inhibition by mediated through HDAC6 activation TGFβ/Smad3 signaling pathway. Our suggests potential therapeutic target for obesity disorders.

Language: Английский

Citations

0
NAT10-mediated N4-acetylcytidine modification in KLF9 mRNA promotes adipogenesis DOI Creative Commons
Xinxing Wan, Linghao Wang, Md. Asaduzzaman Khan

et al.

Cell Death and Differentiation, Journal Year: 2025, Volume and Issue: unknown

Published: March 23, 2025

Abstract Dysfunctional adipogenesis is a major contributor of obesity. N-acetyltransferase 10 (NAT10) plays crucial role in regulating N4-acetylcysteine (ac4C) modification tRNA, 18SrRNA, and mRNA. As the sole “writer” ac4C process, NAT10 enhances mRNA stability translation efficiency. There are few reports on relationship between adipogenesis, as well Our study revealed significant upregulation adipose tissues obese individuals high-fat diet-fed mice. Furthermore, our findings that overexpression promotes while its silencing inhibits both human tissue-derived stem cells (hADSCs) 3T3-L1 cells. These results indicate intimate After mouse (mNAT10), we identified 30 genes exhibited hypo-ac4C downregulation their expression, utilizing combined approach acRIP-sequencing (acRIP-seq) RNA-sequencing (RNA-seq). Among these genes, validated KLF9 target through acRIP-PCR. KLF9, pivotal transcription factor positively regulates adipogenesis. showed further activates CEBPA/B-PPARG pathway. dual-luciferase reporter assay demonstrated can bind to three motifs one motif KLF9. In vivo studies tissue-targeted AAV-NAT10 (AAV-shRNA-mNAT10) tissue expansion Additionally, Remodelin, specific inhibitor, significantly reduced body weight, adipocyte size, mice by inhibiting modification. provide novel insights experimental evidence prevention treatment obesity, highlighting downstream targets potential therapeutic targets.

Language: Английский

Citations

0
Advances in non-Hydroxamate based Histone Deacetylase Inhibitors as Anticancer Agents DOI Open Access

Nadine Wafik,

Maiy Y. Jaballah,

Rabah Serya

et al.

Archives of Pharmaceutical Sciences Ain Shams University, Journal Year: 2024, Volume and Issue: 8(1), P. 133 - 145

Published: April 9, 2024

The carcinogenesis process includes several epigenetic modifications that mainly target the silencing of tumor suppressor genes (TS genes) including ribonucleic acid (RNA) editing, deoxyribonucleic (DNA) hypermethylation and histone modification, either by methylation demethylation, or acetylation deacetylation. Histone deacetylation is one most important responsible for cancer development, thereby, design new selective deacetylase inhibitors (HDACIs) a promising chemotherapeutic target. Up to this time, all HDACIs approved are hydroxamic based. Yet, acids often show drawbacks upon administration, such as poor pharmacokinetic properties, selectivity, multiple toxicities. That's why urge emersion category compounds was crucial. Thereby, non-hydroxamate based attracted widespread attention being part biologically active safer alternative hydroxamate ones. In mini-review, we aim focus on HDACIs, specifically those used anticancer agents, concept behind their development.

Language: Английский

Citations

0