Targeting histone deacetylase and NFκB signaling as a novel therapy for Mucoepidermoid Carcinomas

Wagner, Vivian Petersen; Martins, Manoela Domingues; Martins, Marco Antônio Trevizani; Almeida, Luciana O.; Warner, Kristy A.; Squarize, Cristiane H.; Castilho, Rogerio M.

doi:10.1038/s41598-018-20345-w

Cited by 25 publications

(43 citation statements)

References 68 publications

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“…14 Furthermore, it has been shown that MEC cells are efficiently eliminated using a combination treatment of nuclear factor (NF)-κB and histone deacetylase (HDAC) inhibitors. 15 Thus, BZW1, the IL-6 pathway, NF-κB, and HDAC may represent viable therapeutic targets for MEC therapy.…”

Section: Etiology and Pathology Of Salivary Tumorsmentioning

confidence: 99%

Current State of Knowledge on Salivary Gland Cancers

2018

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Salivary gland cancers (SGCs), categorized as head and neck cancers (HNCs), constitute about 6% of head and neck cancer diagnoses based on estimate by American Head and Neck Society. Salivary gland tumors originate from different glandular cell types and are thus morphologically diverse. These tumors arise from any of the three major and various minor salivary glands. The incidence of SGCs has slowly increased during the last four decades. The etiology of SGCs is mostly unknown; however, specific gene mutations are associated with certain types of salivary tumors. Treatment options include surgical resection, radiation therapy (RT), chemotherapy, and multimodality therapy. HNC patients treated with RT often develop xerostomia and salivary hypofunction due to damaged salivary glands. In this review, we discuss etiology of SGCs, present findings on the role of autophagy in salivary tumorigenesis, review adverse effects of radiation treatment, and examine remedies for restoration of salivary function.

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Section: Etiology and Pathology Of Salivary Tumorsmentioning

confidence: 99%

Current State of Knowledge on Salivary Gland Cancers

2018

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“…Epigenetic modifications can affect HNSCC stem cells, which are an important factor for tumor development and progression 4,30 . CSCs also contribute to radio‐chemotherapy resistance, which can result in tumor relapse.…”

Section: Discussionmentioning

confidence: 99%

Entinostat is a novel therapeutic agent to treat oral squamous cell carcinoma

Marques

Filho

Bezerra

et al. 2020

J Oral Pathology Medicine

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Introduction Alterations of the epigenome may influence cancer initiation and progression. At the cellular level, histones are key regulators of chromatin accessibility and gene transcription; thus, the inhibition of histone deacetylase enzymes (HDACs) constitutes an attractive target for therapy. In this study, we investigated the effects of the HDAC inhibitor entinostat on oral squamous cell carcinoma (OSCC). Materials and Methods We tested the effects of entinostat on OSCC cell lines. Cell viability and growth were analyzed using MTT assay. Cell cycle analysis, cell apoptosis, cancer stem cell (CSC) content, and the concentration of reactive oxygen species (ROS) in OSCC tumor cells were assessed using flow cytometry. The expression of histones and cell cycle regulatory proteins was examined by Western blot. Results The administration of entinostat resulted in reduced proliferation of OSCC cells, followed by cell cycle arrest at the G0/G1 phase, as well as substantial tumor apoptosis. We found an increase in ROS production and significant reductions in CSCs. We also found that entinostat caused increased acetylation histone H3 and histone H4, and changes in the expression of cell cycle‐associated proteins such as p21. Conclusion This study indicates that entinostat is a potential novel therapeutic agent for OSCC by halting tumor proliferation, inducing cytotoxicity and intracellular ROS, and attacking the CSCs.

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“…The treatment of MSC-TRAIL did not have an effect toward an increase in GADD45A expression in the CD133+ CSC sample corresponding to a report that showed low expression of GADD45A in NSCLC tissue samples [133]. However, upregulating the GADD45A gene using histone deacetylase (HDAC) inhibitor [134] may enhance the effect of TRAIL and MSC-TRAIL in NSCLC through negative regulation in NFKB1 expression and the inhibition of CSCs [135,136]. Our findings also indicated that the treatment of MSC-TRAIL downregulated the expression of the HRK gene in the CD133+ CSCs.…”

Section: Discussionmentioning

confidence: 99%

Targeting of CD133+ Cancer Stem Cells by Mesenchymal Stem Cell Expressing TRAIL Reveals a Prospective Role of Apoptotic Gene Regulation in Non-Small Cell Lung Cancer

Fakiruddin

Lim

Nordin

et al. 2019

Cancers

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Mesenchymal stem cells (MSCs) are emerging as vehicles for anti-tumor cytotherapy; however, investigation on its efficacy to target a specific cancer stem cell (CSC) population in non-small cell lung cancer (NSCLC) is lacking. Using assays to evaluate cell proliferation, apoptosis, and gene expression, we investigated the efficacy of MSCs expressing tumour necrosis factor (TNF)-related apoptosis inducing ligand (MSC-TRAIL) to target and destroy CD133+ (prominin-1 positive) NSCLC-derived CSCs. Characterization of TRAIL death receptor 5 (DR5) revealed that it was highly expressed in the CD133+ CSCs of both H460 and H2170 cell lines. The human MSC-TRAIL generated in the study maintained its multipotent characteristics, and caused significant tumor cell inhibition in NSCLC-derived CSCs in a co-culture. The MSC-TRAIL induced an increase in annexin V expression, an indicator of apoptosis in H460 and H2170 derived CD133+ CSCs. Through investigation of mitochondria membrane potential, we found that MSC-TRAIL was capable of inducing intrinsic apoptosis to the CSCs. Using pathway-specific gene expression profiling, we uncovered candidate genes such as NFKB1, BAG3, MCL1, GADD45A, and HRK in CD133+ CSCs, which, if targeted, might increase the sensitivity of NSCLC to MSC-TRAIL-mediated inhibition. As such, our findings add credibility to the utilization of MSC-TRAIL for the treatment of NSCLC through targeting of CD133+ CSCs.

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Targeting histone deacetylase and NFκB signaling as a novel therapy for Mucoepidermoid Carcinomas

Cited by 25 publications

References 68 publications

Current State of Knowledge on Salivary Gland Cancers

Current State of Knowledge on Salivary Gland Cancers

Entinostat is a novel therapeutic agent to treat oral squamous cell carcinoma

Targeting of CD133+ Cancer Stem Cells by Mesenchymal Stem Cell Expressing TRAIL Reveals a Prospective Role of Apoptotic Gene Regulation in Non-Small Cell Lung Cancer

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