Detection of oncometabolite nicotine imine in the nail of oral cancer patients and predicted as an inhibitor of DNMT1

2021 ◽  
Vol 16 ◽  
Author(s):  
Anwesha Deep Dutta ◽  
Ajay Kumar ◽  
Kiran Bharat Lokhande ◽  
Manmohan Mitruka ◽  
K. Venkateswara Swamy ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Oral Cancer ◽  
Cancer Patients ◽  
Dna Methyltransferase ◽  
Biological Fluids ◽  
Md Simulations ◽  
Dynamics Simulation ◽  
Dna Hypomethylation ◽  
Oral Cancer Patients

Background: Nicotine-metabolized product nicotine imine is suggested to play a role in metabolic changes in oral cancer. There is a significant gap in the detection of oncometabolite nicotine imine in biological fluids and nails of oral cancer patients. Oncometabolites are designated as metabolites those are usually elevated in cancer cells over normal cells. Interestingly, a direct or indirect link is missing that establishes a role of nicotine imine in pro-cancer cellular events including global DNA hypomethylation, a potential metabolic-epigenetic axis in oral cancer. Methods: A novel vertical tube gel electrophoresis (VTGE) system assisted purification and liquid chromatography-high resolution mass spectrometry (LC-HRMS) based identification of nicotine imine in the nails of oral cancer patients. Further, nicotine imine was evaluated for its molecular interactions with various methyltransferases including DNA methyltransferase 1 (DNMT1) by molecular docking and molecular dynamics (MD) simulations. Results: Data suggested the presence of nicotine imine in the nails of oral cancer patients. Molecular docking and MD simulations revealed a specific binding affinity by nicotine imine with DNMT1. Binding by nicotine imine is within the CXCC regulatory domain of DNMT1 including key residues as ARG690, PRO574, VAL658, PRO692 and ALA695. Similar binding residues are displayed by DNMT1 inhibitor 5'-Aza-2'-deoxycytidine. Conclusion : Nicotine imine is suggested as a predictive biomarker for oral cancer patients in nails and this finding is a first report. Molecular docking and dynamics simulation propose the role of nicotine imine as an inhibitor of DNMT1. This work supports the involvement of synergistic pro-tumor metabolic-epigenomic axis by nicotine imine that may contribute towards potential mutagenesis of normal squamous epithelium.

scholarly journals Detection of oncometabolites 1-methylnicotinamide, nicotine imine and N-Methylnicotinium in nails of oral cancer patients and prediction of them as modulators of DNMT1

2020 ◽  
Author(s):  
Anwesha Deep Dutta ◽  
Ajay Kumar ◽  
Kiran Lokhande ◽  
Manmohan Mitruka ◽  
Prof. Jayanta K. Pal ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Oral Cancer ◽  
Cancer Patients ◽  
Binding Affinity ◽  
Molecular Interactions ◽  
Specific Binding ◽  
Dynamics Simulation ◽  
Metabolic Adaptation ◽  
Oral Cancer Patients

Background The prominent among various existing views on the role of nicotine and nicotine-metabolized products in Oral squamous cell carcinoma (OSSC) is metabolic adaptation that allows the use of methyl-donor S-adenosylmethionine (SAM) for non-epigenetic purpose including the methylation of nicotinamide and nicotine. In fact, channeling of SAM for generation of 1-methylnicotinamide (1-MNA) and methylated nicotine products is seen as a key event in cancer cells that allows favorable epigenetic states by forcing DNA hypomethylation. A better perception of such events can be appreciated by analyzing samples like nail, which represents a perfect biological material for studying long-term metabolic reflections of the body. Methods Potential nicotine-metabolized products and 1-MNA in nails of OSCC patients were analyzed by using a novel approach of Vertical tube gel electrophoresis (VTGE)- assisted purification followed by their identification by LC-HRMS. Further, these identified nicotine metabolized products and 1-MNA were evaluated for their molecular interactions with known methyltransferases including cytosolic nicotinamide methyltransferase (NNMT), DNA methyltransferase (DNMT)1 and histone methyltransferases by molecular docking and molecular dynamics simulation (MDS) analyses. Results Our data suggests the presence of N-methylnicotinium ion and nicotine imine in the nail samples of OSCC patients. Further, 1-MNA is also detected in the nails as a major enzymatic product of a known detoxifying enzyme NNMT. Molecular docking of all nicotine and nicotine metabolized products with DNMT1revealed a specific binding affinity of nicotine imine only with a -6.2 Kcal/Mol docking energy. Importantly, binding of nicotine imine is within the CXCC regulatory domain of DNMT1 and it displays molecular interactions with the key amino acid residues, namely ARG690, PRO574, VAL658, PRO692 and ALA695. Furthermore, MDS data corroborated well with the specific binding affinity of nicotine imine to DNMT1 obtained by docking analysis. Conclusion Identification of N-methylnicotinium ion, nicotine imine and 1-MNA in nail samples indicates their potential as predictive and detectable biomarkers for OSCC. Molecular docking and MDS data lead us to propose a role of nicotine imine in modulating the activity of DNMT1. These data further suggest a novel understanding on the role of nicotine metabolized products in modulating DNA methylation that may contribute to tumorigenicity in oral cancer patients.

Prognostic role of Oct4, CD44 and c-Myc in radio–chemo-resistant oral cancer patients and their tumourigenic potential in immunodeficient mice

2015 ◽  
Vol 20 (1) ◽  
pp. 43-56 ◽  
Author(s):  
Sharada Sawant ◽  
Ravindran Gokulan ◽  
Harsh Dongre ◽  
Milind Vaidya ◽  
Devendra Chaukar ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Cancer Patients ◽  
Prognostic Role ◽  
Immunodeficient Mice ◽  
Oral Cancer Patients

scholarly journals Droplet Digital PCR Analysis of Liquid Biopsy Samples Unveils the Diagnostic Role of hsa-miR-133a-3p and hsa-miR-375-3p in Oral Cancer

Biology ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 379
Author(s):  
Salvatore Crimi ◽  
Luca Falzone ◽  
Giuseppe Gattuso ◽  
Caterina Maria Grillo ◽  
Saverio Candido ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Digital Pcr ◽  
Droplet Digital Pcr ◽  
Pcr Analysis ◽  
Screening Programs ◽  
Diagnostic Potential ◽  
Oral Cancer Patients

Despite the availability of screening programs, oral cancer deaths are increasing due to the lack of diagnostic biomarkers leading to late diagnosis and a poor prognosis. Therefore, there is an urgent need to discover novel effective biomarkers for this tumor. On these bases, the aim of this study was to validate the diagnostic potential of microRNAs (miRNAs) through the analysis of liquid biopsy samples obtained from ten oral cancer patients and ten healthy controls. The expression of four selected miRNAs was evaluated by using droplet digital PCR (ddPCR) in a pilot cohort of ten oral cancer patients and ten healthy donors. Bioinformatics analyses were performed to assess the functional role of these miRNAs. The expression levels of the predicted down-regulated hsa-miR-133a-3p and hsa-miR-375-3p were significantly reduced in oral cancer patients compared to normal individuals while no significant results were obtained for the up-regulated hsa-miR-503-5p and hsa-miR-196a-5p. ROC analysis confirmed the high sensitivity and specificity of hsa-miR-375-3p and hsa-miR-133a-3p. Therefore, both miRNAs are significantly down-regulated in cancer patients and can be used as biomarkers for the early diagnosis of oral cancer. The analysis of circulating miRNAs in a larger series of patients is mandatory to confirm the results obtained in this pilot study.

Abstract 3700: Role of salivary miRNAs and their target genes in oral cancer patients as a potential diagnostic tool

2020 ◽  
Author(s):  
Muhammad Jawad Khan ◽  
Andleeb Zahra ◽  
Ghulam Rabia ◽  
Syeda Aba Ali ◽  
Shanza Sahar ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Cancer Patients ◽  
Diagnostic Tool ◽  
Target Genes ◽  
Oral Cancer Patients

scholarly journals Role of Monocyte Count and Neutrophil-to-Lymphocyte Ratio in Survival of Oral Cancer Patients

2016 ◽  
Vol 21 (01) ◽  
pp. 21-27 ◽  
Author(s):  
Saurabh Bobdey ◽  
Balasubramaniam Ganesh ◽  
Prabhashankar Mishra ◽  
Aanchal Jain
Keyword(s):  
Oral Cancer ◽  
Cancer Patients ◽  
Neutrophil To Lymphocyte Ratio ◽  
Monocyte Count ◽  
Lymphocyte Ratio ◽  
Oral Cancer Patients

scholarly journals Detection of Nail Oncometabolite SAICAR in Oral Cancer and Its Molecular Interactions with PKM2 Enzyme

2021 ◽  
Author(s):  
Rushikesh Patel ◽  
Ajay Kumar ◽  
Kiran Bharat Lokhande ◽  
K. Venkateswara Swamy ◽  
Prof. Sachin C Sarode ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Oral Cancer ◽  
Early Detection ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Molecular Interactions ◽  
Biological Fluids ◽  
Metabolic Adaptations ◽  
Oral Cancer Patients ◽  
Low Glucose

<p>Oncometabolites are known to drive metabolic adaptations in oral cancer. These oncometabolites serve as biomarkers for early detection of oral cancer. Among potential oncometabolite, SAICAR is one of them that support growth and invasiveness of cancer cells. SAICAR has been reported to activate Pyruvate Kinase M2 (PKM2) enzyme, which in turn favors the survival of cancer cells in low glucose tumor microenvironment. There is a significant gap in detection of SAICAR in biological fluids/materials including nails of oral cancer patients. </p>

The Role of Socioeconomic Status and Literacy in the treatment delay in Oral Cancer patients Visiting Mayo Hospital

2021 ◽  
Vol 15 (8) ◽  
pp. 1785-1787
Author(s):  
Ahmad Liaquat ◽  
Rabia Naseer ◽  
Muhammad Rashid ◽  
Saqib Mehmood Khan ◽  
Ehsan Ul Haq ◽  
...  
Keyword(s):  
Socioeconomic Status ◽  
Oral Cancer ◽  
Cancer Patients ◽  
Treatment Delay ◽  
Stage Iii ◽  
Care Hospital ◽  
Low Socioeconomic ◽  
Oral Cancer Patients ◽  
Late Stages

Background: One of the most important prognostic factors of oral cancer is the stage at the time of diagnosis. Unfortunately, most of the patients present in the late stages (stage III and IV). Aim: To assess the role of socioeconomic status and literacy in the treatment delay in patients of oral cancer. By identifying their role, we can educate the general public and healthcare doctors to detect and treat oral cancer. Method: This was a prospective study conducted in the Mayo hospital, a tertiary care hospital of Pakistan, from June 2018 to June 2020. Results: Out of 120 patients, 84 (70%) were males and 36 (30%) were females. The age range was 14 to 85 years. One hundred and eight patients (90%) presented with the late stages (stage III and IV). These late-stage presenter patients belonged to the low socioeconomic status (88.88%) and 83.33% of them were illiterate (<high school education). Only twelve patients (10%) presented with the early stage at the time of diagnosis. Conclusion: Low socioeconomic and lack of education have a significant association with the late presentation of oral cancer patients in the Pakistani population. Keywords: squamous cell carcinoma, treatment delay, socioeconomic status

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