Emerging role of cellular senescence in the pathogenesis of oral submucous fibrosis and its malignant transformation

Sharma, Mohit; Hunter, Keith; Fonseca, Felipe Paiva; Radhakrishnan, Raghu

doi:10.1002/hed.26805

Cited by 17 publications

(13 citation statements)

References 64 publications

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“…Similar results have been obtained in vivo following administration of apigenin daily for 8 weeks to a d-galactose-induced aging mouse model [ 309 ]. Moreover, thanks to its ability to inhibit the SASP and to interfere with the anti-apoptotic pathways, which are generally upregulated in senescent cancer cells, apigenin has been proposed as an adjuvant therapy for tumours, with promising results [ 237 , 310 , 311 ].…”

Section: Resultsmentioning

confidence: 99%

The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence

et al. 2022

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Cellular senescence is an irreversible state of cell cycle arrest occurring in response to stressful stimuli, such as telomere attrition, DNA damage, reactive oxygen species, and oncogenic proteins. Although beneficial and protective in several physiological processes, an excessive senescent cell burden has been involved in various pathological conditions including aging, tissue dysfunction and chronic diseases. Oxidative stress (OS) can drive senescence due to a loss of balance between pro-oxidant stimuli and antioxidant defences. Therefore, the identification and characterization of antioxidant compounds capable of preventing or counteracting the senescent phenotype is of major interest. However, despite the considerable number of studies, a comprehensive overview of the main antioxidant molecules capable of counteracting OS-induced senescence is still lacking. Here, besides a brief description of the molecular mechanisms implicated in OS-mediated aging, we review and discuss the role of enzymes, mitochondria-targeting compounds, vitamins, carotenoids, organosulfur compounds, nitrogen non-protein molecules, minerals, flavonoids, and non-flavonoids as antioxidant compounds with an anti-aging potential, therefore offering insights into innovative lifespan-extending approaches.

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Section: Resultsmentioning

confidence: 99%

The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence

et al. 2022

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“…The atrophic epithelium can be attributed to senescence of epithelial cells and leads to the downregulation of basal stemness [90]. The reduced vascularity in OSMF may be attributable to senescence of endothelial cells, as suggested in a recent pathogenetic model [91]. Biologically active areca nut alkaloids stimulate fibroblasts to increase collagen synthesis and, concurrently, there is decreased activity of collagenases and reduced collagen degradation.…”

Section: Cellular Senescence Is Associated With Osmfmentioning

confidence: 96%

“…Biologically active areca nut alkaloids stimulate fibroblasts to increase collagen synthesis and, concurrently, there is decreased activity of collagenases and reduced collagen degradation. These changes result in fibrosis of the underlying submucosa and are further associated with chronic inflammation and hypoxia [91].…”

Section: Cellular Senescence Is Associated With Osmfmentioning

confidence: 99%

“…Therefore, there appears to be a progressive accumulation of senescent stromal cells in OSMF. Mechanistically, the same authors later showed that areca nut alkaloids induce both irreparable DNA damage and senescence in fibroblasts in vitro which creates a favourable environment for tumour progression [91]. Intrinsic oxidative damage was proposed as a potential cause of senescence in vitro and in vivo in OSMF, and, importantly, the use of anti-oxidants was capable of reducing the frequency of senescent cells [92].…”

Section: Cellular Senescence Is Associated With Osmfmentioning

confidence: 99%

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Molecular Mechanisms of Malignant Transformation of Oral Submucous Fibrosis by Different Betel Quid Constituents—Does Fibroblast Senescence Play a Role?

Zhang

Chua

Dang

et al. 2022

IJMS

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Betel quid (BQ) is a package of mixed constituents that is chewed by more than 600 million people worldwide, particularly in Asia. The formulation of BQ depends on a variety of factors but typically includes areca nut, betel leaf, and slaked lime and may or may not contain tobacco. BQ chewing is strongly associated with the development of potentially malignant and malignant diseases of the mouth such as oral submucous fibrosis (OSMF) and oral squamous cell carcinoma (OSCC), respectively. We have shown recently that the constituents of BQ vary geographically and that the capacity to induce disease reflects the distinct chemical composition of the BQ. In this review, we examined the diverse chemical constituents of BQ and their putative role in oral carcinogenesis. Four major areca alkaloids—arecoline, arecaidine, guvacoline and guvacine—together with the polyphenols, were identified as being potentially involved in oral carcinogenesis. Further, we propose that fibroblast senescence, which is induced by certain BQ components, may be a key driver of tumour progression in OSMF and OSCC. Our study emphasizes that the characterization of the detrimental or protective effects of specific BQ ingredients may facilitate the development of targeted BQ formulations to prevent and/or treat potentially malignant oral disorders and oral cancer in BQ users.

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“…There are many substances secreted by senescent cells. First, these cells secrete proteins such as interleukin (IL)-1, IL-6, and IL-8 [ 40 ], which can affect surrounding cells by cell surface receptors, chemokines such as CXCL family-1/2/4/5/6/8/12, MCP-2/4, CCL family members 2/3/4/5/7/8/13/16/20/26, and CXCR-2 binding factor [ 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ], and insulin-like growth factor (IGF) pathway components (IGFBP-2/3/4/5/6 and their regulators IGFBP-rP1/rP2/7), which influence the microenvironment of senescent cells [ 49 , 50 , 51 , 52 , 53 ]. Second, senescent cells secrete soluble factors such as colony-stimulating factors (CSFs), including granulocyte macrophage-CSF and G-CSF, osteoprotegerin, prostaglandin E2 (PGE2), and COX-2, which is the enzyme responsible for the production of PGE2 and other prostaglandins [ 46 , 50 , 54 ].…”

Section: Aging Pmcs Promote Tumor Progression In the Peritoneal Cavitymentioning

confidence: 99%

Role of Peritoneal Mesothelial Cells in the Progression of Peritoneal Metastases

Guo

2022

Cancers

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Peritoneal metastatic cancer comprises a heterogeneous group of primary tumors that originate in the peritoneal cavity or metastasize into the peritoneal cavity from a different origin. Metastasis is a characteristic of end-stage disease, often indicative of a poor prognosis with limited treatment options. Peritoneal mesothelial cells (PMCs) are a thin layer of cells present on the surface of the peritoneum. They display differentiated characteristics in embryonic development and adults, representing the first cell layer encountering peritoneal tumors to affect their progression. PMCs have been traditionally considered a barrier to the intraperitoneal implantation and metastasis of tumors; however, recent studies indicate that PMCs can either inhibit or actively promote tumor progression through distinct mechanisms. This article presents a review of the role of PMCs in the progression of peritoneum implanted tumors, offering new ideas for therapeutic targets and related research.

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Emerging role of cellular senescence in the pathogenesis of oral submucous fibrosis and its malignant transformation

Cited by 17 publications

References 64 publications

The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence

The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence

Molecular Mechanisms of Malignant Transformation of Oral Submucous Fibrosis by Different Betel Quid Constituents—Does Fibroblast Senescence Play a Role?

Role of Peritoneal Mesothelial Cells in the Progression of Peritoneal Metastases

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