Undetectable Free Aromatic Amino Acids in Nails of Breast Carcinoma: Biomarker Discovery by a Novel Metabolite Purification VTGE System

Mitruka, Manmohan; Gore, Charusheela; Kumar, Ajay; Sarode, Sachin C.; Sharma, Nilesh Kumar

doi:10.3389/fonc.2020.00908

Cited by 15 publications

(8 citation statements)

References 46 publications

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“…The primary goals were to study the nail lysate in the context of nicotine and nicotine-derived metabolites with the assistance of a novel vertical tube gel electrophoresis (VTGE) metabolite purification system and identification of these metabolites with the help of LC-HRMS (Sharma et al, 2019; Mitruka et al, 2020). A working model of novel VTGE system is presented in Figure S1.…”

Section: Materals and Methodsmentioning

confidence: 99%

“…The authors agree that reported novel approach on identification of nail metabolites also detects other routinely used drugs and metabolic products as shown in the TIC of healthy and OSCC subjects. Our lab and existing literature have attempted to address the accumulation of various types of drugs, metabolized drugs, environmental toxins (Oyoo-Okoth et al, 2010; Krumbiegel et al, 2016; Mitruka et al, 2020; Sharma et al, 2020). However, this finding presents a first report on the detection of oncometabolites such as 1-MNA, nicotine imine and N-methylnicotinium ion and their possible link with the metabolic-epigenetic signaling axis.…”

Section: Sam Dna Methylation and Cancermentioning

confidence: 99%

“…Nail has been considered as the best material for bio-monitoring of the pathophysiological changes over a period of time. Nail clipping samples reflect the biochemical changes over 12 to 18 months period of time, and therefore it is most commonly used for detection of prolonged exposure of external noxious agents to the body (Oyoo-Okoth et al, 2010; Krumbiegel et al, 2016; Mitruka et al, 2020; Sharma et al, 2020). Interestingly, S-nicotine metabolized products including nicotine imine and N-methylnicotinium ion are reported to some extent in different tissues and biological fluids (Nwosu et al, 1988; Berkman et al, 1995; von Weymarn et al, 2002; Kilgore et al, 2013; Jeltsch et al, 2016; Miletić et al, 2017; Yu et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

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

Dutta

Kumar

Lokhande

et al. 2020

Preprint

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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.

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Section: Materals and Methodsmentioning

confidence: 99%

Section: Sam Dna Methylation and Cancermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Dutta

Kumar

Lokhande

et al. 2020

Preprint

Self Cite

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“…In the case of nails, even post-mortem specimens can be successfully collected and investigated [72]. According to the cited study [36], nails are a promising matrix for evaluating cancer-related alterations in amino acid metabolism in patients.…”

Section: Other Matricesmentioning

confidence: 99%

“…Kynurenine, which is a metabolized product of tryptophan, may promote differentiation of T regulatory cells, which might help in cancer-mediated evasion of the immune system [94]. The decreased levels of phenylalanine mentioned in a few studies [36,40,46] might be caused by the increased demand for this amino acid by cancer cells [95]. As proline can be used as an energy source and as a precursor for protein synthesis, the need for this amino acid is increased and thus, proline biosynthesis is increased.…”

Section: Breast Cancermentioning

confidence: 99%

Free Amino Acid Alterations in Patients with Gynecological and Breast Cancer: A Review

et al. 2021

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Gynecological and breast cancers still remain a significant health problem worldwide. Diagnostic methods are not sensitive and specific enough to detect the disease at an early stage. During carcinogenesis and tumor progression, the cellular need for DNA and protein synthesis increases leading to changes in the levels of amino acids. An important role of amino acids in many biological pathways, including biosynthesis of proteins, nucleic acids, enzymes, etc., which serve as an energy source and maintain redox balance, has been highlighted in many research articles. The aim of this review is a detailed analysis of the literature on metabolomic studies of gynecology and breast cancers with particular emphasis on alterations in free amino acid profiles. The work includes a brief overview of the metabolomic methodology and types of biological samples used in the studies. Special attention was paid to the possible role of selected amino acids in the carcinogenesis, especially proline and amino acids related to its metabolism. There is a clear need for further research and multiple external validation studies to establish the role of amino acid profiling in diagnosing gynecological and breast cancers.

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Polypyrrole/carbon dot nanocomposite as an electrochemical biosensor for liquid biopsy analysis of tryptophan in the human serum of normal and breast cancer women

et al. 2023

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Liquid biopsy analysis represents a suitable alternative analysis procedure in several cases where no tumor tissue is available or in poor patient conditions. Amino acids can play a crucial role in aiding cancer diagnosis. Monitoring of tryptophan (Trp) catabolism can aid in tracking cancer progression. Therefore, a novel nanocomposite was fabricated using overoxidized polypyrrole film doped with nano-carbon dots (nano-CDs) on the pencil graphite electrode (PGE) surface for sensitive evaluation of Trp in human serum. Using square wave voltammetry (SWV), the overoxidized polypyrrole/carbon dots/pencil graphite electrode (Ov-Ox PPy/CDs/PGE) achieved excellent electrochemical catalytic activity for evaluating Trp. The modified electrode, known as Ov-Ox PPy/CDs/PGE, demonstrated superior electrochemical catalytic activity compared to bare PGE, CDs/PGE, PPy/PGE, and PPy/CDs/PGE for evaluation of Trp. The method’s excellent sensitivity was confirmed by the low limits of detection (LOD = 0.003 μmol L−1) and limit of quantitation (LOQ = 0.009 μmol L−1). The biosensor that was developed can measure tryptophan (Trp) levels in the serum of both healthy individuals and female breast cancer patients with high accuracy and sensitivity. The results indicate that there is a significant difference, as shown by the F-test, between healthy individuals and those with breast cancer. This suggests that Trp amino acid could be an essential biomarker for cancer diagnosis. Consequently, liquid biopsy analysis presents a valuable opportunity for early disease detection, particularly for cancer. Graphical abstract

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Undetectable Free Aromatic Amino Acids in Nails of Breast Carcinoma: Biomarker Discovery by a Novel Metabolite Purification VTGE System

Cited by 15 publications

References 46 publications

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

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

Free Amino Acid Alterations in Patients with Gynecological and Breast Cancer: A Review

Polypyrrole/carbon dot nanocomposite as an electrochemical biosensor for liquid biopsy analysis of tryptophan in the human serum of normal and breast cancer women

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