Can We Efficiently Target HDAC in Cancer?

Kiesslich, Tobias; Neureiter, Daniel

doi:10.3390/cancers14164058

Cited by 4 publications

(3 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As we know that the high expression of HDACs is strongly correlated with the proliferation, migration, invasion and metastasis in cancer subtypes 9 , 10 , 13 , 84 . The overexpression of HDAC1 and HDAC3 promotes proliferation, differentiation and metastasis in colon and prostate cancer 85 – 88 .…”

Section: Discussionmentioning

confidence: 99%

“…The role of HDACs in the initiation, progression, invasion, and metastasis of various cancer subtypes has been well studied 8 – 10 . In addition, the contribution of HDACs has also been well documented in various pathophysiological conditions like cardiovascular diseases, diabetes, neurodegenerative disorders, inflammatory diseases, learning-memory dysfunctions, and Huntington’s disease 11 , 12 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Repurposing of neprilysin inhibitor ‘sacubitrilat’ as an anti-cancer drug by modulating epigenetic and apoptotic regulators

Kumbhar,

Nimal,

Patil

et al. 2023

Sci Rep

View full text Add to dashboard Cite

Modifications in the epigenetic landscape have been considered a hallmark of cancer. Histone deacetylation is one of the crucial epigenetic modulations associated with the aggressive progression of various cancer subtypes. Herein, we have repurposed the neprilysin inhibitor sacubitrilat as a potent anticancer agent using in-silico protein–ligand interaction profiler (PLIP) analysis, molecular docking, and in vitro studies. The screening of PLIP profiles between vorinostat/panobinostat and HDACs/LTA4H followed by molecular docking resulted in five (Sacubitrilat, B65, BDS, BIR, and NPV) FDA-approved, experimental and investigational drugs. Sacubitrilat has demonstrated promising anticancer activity against colorectal cancer (SW-480) and triple-negative breast cancer (MDA-MB-231) cells, with IC50 values of 14.07 μg/mL and 23.02 μg/mL, respectively. FACS analysis revealed that sacubitrilat arrests the cell cycle at the G0/G1 phase and induces apoptotic-mediated cell death in SW-480 cells. In addition, sacubitrilat inhibited HDAC isoforms at the transcriptomic level by 0.7–0.9 fold and at the proteomic level by 0.5–0.6 fold as compared to the control. Sacubitrilat increased the protein expression of tumor-suppressor (p53) and pro-apoptotic makers (Bax and Bid) by 0.2–2.5 fold while decreasing the expression of anti-apoptotic Bcl2 and Nrf2 proteins by 0.2–0.5 fold with respect to control. The observed cleaved PARP product indicates that sacubitrilat induces apoptotic-mediated cell death. This study may pave the way to identify the anticancer potential of sacubitrilat and can be explored in human clinical trials.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Repurposing of neprilysin inhibitor ‘sacubitrilat’ as an anti-cancer drug by modulating epigenetic and apoptotic regulators

Kumbhar,

Nimal,

Patil

et al. 2023

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Moreover, elevated levels of classical HDACs have been linked to advanced disease progression and unfavorable patient outcomes [28]. When histone tails are highly acetylated, they adopt a more relaxed conformation with DNA, potentially leading to the overexpression of cancer-related genes [29]. Recent advancements show that HDACs can inhibit DNA repair, induce cell apoptosis and acetylate non-histone proteins [30,31].…”

Section: Introductionmentioning

confidence: 99%

Targeting histone deacetylases in head and neck squamous cell carcinoma: molecular mechanisms and therapeutic targets

Xu,

Hou,

et al. 2024

J Transl Med

View full text Add to dashboard Cite

The onerous health and economic burden associated with head and neck squamous cell carcinoma (HNSCC) is a global predicament. Despite the advent of novel surgical techniques and therapeutic protocols, there is an incessant need for efficacious diagnostic and therapeutic targets to monitor the invasion, metastasis and recurrence of HNSCC due to its substantial morbidity and mortality. The differential expression patterns of histone deacetylases (HDACs), a group of enzymes responsible for modifying histones and regulating gene expression, have been demonstrated in neoplastic tissues. However, there is limited knowledge regarding the role of HDACs in HNSCC. Consequently, this review aims to summarize the existing research findings and explore the potential association between HDACs and HNSCC, offering fresh perspectives on therapeutic approaches targeting HDACs that could potentially enhance the efficacy of HNSCC treatment. Additionally, the Cancer Genome Atlas (TCGA) dataset, CPTAC, HPA, OmicShare, GeneMANIA and STRING databases are utilized to provide supplementary evidence on the differential expression of HDACs, their prognostic significance and predicting functions in HNSCC patients. Graphical Abstract

show abstract

A review of progress in o-aminobenzamide-based HDAC inhibitors with dual targeting capabilities for cancer therapy

Zhang

Huang

Tian

et al. 2023

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

Can We Efficiently Target HDAC in Cancer?

Abstract: According to the hallmarks of cancer, typical processes of human cancer initiation, progression, and metastasis are essentially influenced by pathologic epigenetic deregulations via DNA methylation and/or histone modification [...]

Cited by 4 publications

References 19 publications

Repurposing of neprilysin inhibitor ‘sacubitrilat’ as an anti-cancer drug by modulating epigenetic and apoptotic regulators

Repurposing of neprilysin inhibitor ‘sacubitrilat’ as an anti-cancer drug by modulating epigenetic and apoptotic regulators

Targeting histone deacetylases in head and neck squamous cell carcinoma: molecular mechanisms and therapeutic targets

A review of progress in o-aminobenzamide-based HDAC inhibitors with dual targeting capabilities for cancer therapy

Contact Info

Product

Resources

About