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

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 ß-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.

Quantification of betel quid hygroscopicity in context to saliva: A proof of concept for future studies.

The physical and chemical properties of various constitutional ingredients of betel quid (BQ) are well known in the literature. However, BQ as a whole has been rarely investigated for identifying its physical properties that can impact and modulate the disease progression of various pathologies, mainly oral submucous fibrosis (OSMF). It is quite conceivable that in the oral cavity environment, the amalgamated BQ might absorb saliva by virtue of its hygroscopic properties. As a proof of concept, we developed a methodology to quantify the hygroscopicity of the 'whole BQ' when it is mixed with saliva. To the best of our knowledge, this is the first study to report and quantify the hygroscopicity of BQ when mixed with saliva, and this forms a proof of concept for future implications in the pathogenesis of various pathologies.