Do osmotic pressure and hygroscopicity of areca nut related products drive extracellular fluid loss and condensation of collagen bundles in oral submucous fibrosis?

Sarode, Sachin C.; Sharma, Nilesh Kumar; Bhatkar, Devyani

doi:10.1016/j.mehy.2022.110836

Cited by 1 publication

(2 citation statements)

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“…Our findings on SABFI-derived organic acids as potential inhibitors of TET2 agree with current views on the metabolic-epigenomic axis in cancer cells [ 13 - 18 ]. Findings suggest a high accumulation of fumarate and succinate in cancer cells [ 30 - 37 , 39 , 50 - 53 ]. Fumarate and succinate are suggested for their inhibitory effects upon DNA demethylases and histone demethylases lysine-specific demethylase 4A (KDM4A) and KDM4B.…”

Section: Discussionmentioning

confidence: 99%

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Organic Acids Derived from Saliva-amalgamated Betel Quid Filtrate Are Predicted as a Ten-eleven Translocation-2 Inhibitor

Bhatkar,

Ananda,

Lokhande

et al. 2023

J Cancer Prev

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There is a lack of evidence regarding the use of betel quid (BQ) and its potential contribution to oral cancer. Limited attention has been directed towards investigating the involvement of BQ-derived organic acids in the modulation of metabolic-epigenomic pathways associated with oral cancer initiation and progression. We employed novel protocol for preparing saliva-amalgamated BQ filtrate (SABFI) that mimics the oral cavity environment. SABFI and saliva control were further purified by an in-house developed vertical tube gel electrophoresis tool. The purified SABFI was then subjected to liquid chromatography-high resolution mass spectrometry analysis to identify the presence of organic acids. Profiling of SABFI showed a pool of prominent organic acids such as citric acid. malic acid, fumaric acid, 2-methylcitric acid, 2-hydroxyglutarate, cis- aconitic acid, succinic acid, 2-hydroxyglutaric acid lactone, tartaric acid and β-ketoglutaric acid. SABFI showed anti-proliferative and early apoptosis effects in oral cancer cells. Molecular docking and molecular dynamics simulations predicted that SABFI-derived organic acids as potential inhibitors of the epigenetic demethylase enzyme, Ten-Eleven Translocation-2 (TET2). By binding to the active site of α-ketoglutarate, a known substrate of TET2, these organic acids are likely to act as competitive inhibitors. This study reports a novel approach to study SABFI-derived organic acids that could mimic the chemical composition of BQ in the oral cavity. These SABFI-derived organic acids projected as inhibitors of TET2 and could be explored for their role oral cancer.

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Section: Discussionmentioning

confidence: 99%

“…Furthermore, SABFI was estimated by weight/volume analysis, and a 3 mg/mL stock of SABFI was prepared and stored at –20°C for further investigation and cell-based assays. As a control, saliva without BQ was processed and prepared for analysis and cell-based assays [ 32 ].…”

Section: Methodsmentioning

confidence: 99%