Epigenetic modulation and understanding of HDAC inhibitors in cancer therapy

Ramaiah, Madhuvanthi; Tangutur, Anjana Devi; Reddy, M. Rajasekhar

doi:10.1016/j.lfs.2021.119504

Cited by 186 publications

(101 citation statements)

References 233 publications

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“…Eleven zinc‐dependent enzymes form classes I, II, and IV, and seven NAD‐dependent sirtuins are class III [ 1 ]. It has become clear that HDAC inhibitors (HDACi) will only develop their therapeutic potential in combination treatments [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Mechanistic insights into p53‐regulated cytotoxicity of combined entinostat and irinotecan against colorectal cancer cells

et al. 2021

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Late-stage colorectal cancer (CRC) is still a clinically challenging problem. The activity of the tumor suppressor p53 is regulated via posttranslational modifications (PTMs). While the relevance of p53 Cterminal acetylation for transcriptional regulation is well-defined, it is unknown whether this PTM controls mitochondrially mediated apoptosis directly. We used wild-type p53 or p53-negative human CRC cells, cells with acetylation-defective p53, transformation assays, CRC organoids, and xenograft mouse models to assess how p53 acetylation determines cellular stress responses. The topoisomerase-1 inhibitor irinotecan induces acetylation of several lysine residues within p53. Inhibition of histone deacetylaces (HDACs) with the class I HDAC inhibitor entinostat synergistically triggers mitochondrial damage and apoptosis in irinotecan-treated p53-positive CRC cells. This specifically relies on the C-terminal acetylation of p53 by CREB binding protein (CBP)/p300 and the presence of C-terminally acetylated p53 in complex with the pro-apoptotic BCL2 antagonist/killer (BAK) protein. This control of C-terminal acetylation by HDACs can mechanistically explain why combinations of irinotecan and entinostat represent clinically tractable agents for the therapy of p53-proficient CRC.

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Section: Introductionmentioning

confidence: 99%

Mechanistic insights into p53‐regulated cytotoxicity of combined entinostat and irinotecan against colorectal cancer cells

et al. 2021

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“…[ 29 ]. As the therapies which target the immune checkpoint molecule against cervical cancer have been emerging in the past decade [ 30 , 31 ], the effectiveness is now reaching a plateau [ 32 , 33 ]. Thus, understanding and figuring out the influence of HDACs on the cervical cancer progression would contribute to develop the potential preferable therapeutic treatment.…”

Section: Discussionmentioning

confidence: 99%

HDAC10 Inhibits Cervical Cancer Progression through Downregulating the HDAC10-microRNA-223-EPB41L3 Axis

Zhou

Yao

et al. 2022

Journal of Oncology

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Background. Although the tumorigenesis of cervical cancer (CC) has been widely investigated and recognized, the study of the systematic impact of histone deacetylase 10 (HDAC10), microRNA, and downstream molecular mechanisms in CC is still limited. Herein, cervical cancer, precancer lesions, and normal cervical tissues were collected to test the expression level of HDAC10, miR-223, and EPB41L3. The mechanism of HDAC10, miR-223, and EPB41L3 was interpreted in cervical cancer cells after HDAC10, miR-223, or EPB41L3 expression was altered. Results. HDAC10 was poorly expressed in cervical cancer and precancer lesions, while miR-223 was highly expressed in cervical cancer. HDAC10 bound to miR-223, and miR-223 targeted EPB41L3. HDAC10 depressed the invasion property and tumorigenesis of cervical cancer via downregulating miR-223 and subsequently targeting EPB41L3. Conclusion. The study clarifies that HDAC10 inhibits cervical cancer by downregulating miR-223 and subsequently targeting EPB41L3 expression, which might provide a new insight for management upon cervical cancer and precancer lesions.

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“…So far, 4 HDIs have been approved by The Food and Drug Administration (FDA): vorinostat (SAHA) in cutaneous T-cell lymphoma (CTLC) treatment, belinostat, and romidepsin in peripheral T-cell lymphoma (PTCL) treatment, and panobinostat in multiple myeloma treatment [32]. However, these inhibitors are used in cancer therapy; they are not selective against specific HDAC isoforms, resulting in serve side effects [33]. Nowadays, many other HDIs are tested in preclinical trials, and some of them seem to be promising anti-cancer tools.…”

Section: Of 20mentioning

confidence: 99%

Deacetylation of Transcription Factors in Carcinogenesis

Hałasa

Adamczuk

et al. 2021

IJMS

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Reversible Nε-lysine acetylation/deacetylation is one of the most common post-translational modifications (PTM) of histones and non-histone proteins that is regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). This epigenetic process is highly involved in carcinogenesis, affecting histone and non-histone proteins’ properties and their biological functions. Some of the transcription factors, including tumor suppressors and oncoproteins, undergo this modification altering different cell signaling pathways. HDACs deacetylate their targets, which leads to either the upregulation or downregulation of proteins involved in the regulation of cell cycle and apoptosis, ultimately influencing tumor growth, invasion, and drug resistance. Therefore, epigenetic modifications are of great clinical importance and may constitute a new therapeutic target in cancer treatment. This review is aimed to present the significance of HDACs in carcinogenesis through their influence on functions of transcription factors, and therefore regulation of different signaling pathways, cancer progression, and metastasis.

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Epigenetic modulation and understanding of HDAC inhibitors in cancer therapy

Cited by 186 publications

References 233 publications

Mechanistic insights into p53‐regulated cytotoxicity of combined entinostat and irinotecan against colorectal cancer cells

Mechanistic insights into p53‐regulated cytotoxicity of combined entinostat and irinotecan against colorectal cancer cells

HDAC10 Inhibits Cervical Cancer Progression through Downregulating the HDAC10-microRNA-223-EPB41L3 Axis

Deacetylation of Transcription Factors in Carcinogenesis

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