Organic Acids Derived from Saliva-amalgamated Betel Quid Filtrate Are Predicted as a Ten-eleven Translocation-2 Inhibitor
10.15430/JCP.2023.28.3.115
- Author:
Devyani BHATKAR
1
;
Nistha ANANDA
;
Kiran Bharat LOKHANDE
;
Kratika KHUNTETA
;
Priyadarshini JAIN
;
Ameya HEBALE
;
Sachin C. SARODE
;
Nilesh Kumar SHARMA
Author Information
1. Cancer and Translational Research Lab, Dr. D. Y. Patil Biotechnology & Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, India
- Publication Type:Original Article
- From:Journal of Cancer Prevention
2023;28(3):115-130
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
