The Concentration Levels of ATP in Oral Squamous Cell Carcinoma Tissues and Risk Habits Involved: An Experimental Study
- Authors
-
-
Emmanuel Mendoza
Research Institute of Dentistry, Comprehensive Dental Clinics Department, University Center of Health Sciences, University of Guadalajara, Guadalajara 44100, Mexico -
José Roberto Prieto Correa
Research Institute in Chronic Degenerative Diseases, Division of Basic Disciplines, University Center of Health Sciences, University of Guadalajara, Guadalajara 44100, Mexico -
José Alfonso Cruz Ramos
Research Coordination of Jalisciense Institute of Cancerology. Zapopan, Jal; C. Puerto Guaymas 418, Miramar -
Paola Monserrat Zepeda Olmos
Research Coordination of Jalisciense Institute of Cancerology. Zapopan, Jal; C. Puerto Guaymas 418, Miramar -
Juan José Soto Ávila
Service of Head and Neck Oncology Surgery; Jalisciense Institute of Cancerology. Zapopan Jal; C. Puerto Guaymas 418, Miramar -
Sandra López Verdín
Research Institute of Dentistry, Comprehensive Dental Clinics Department, University Center of Health Sciences, University of Guadalajara, Guadalajara 44100, Mexico
-
- Keywords:
- Adenosine Triphosphate, Energy Metabolism, Carcinogenesis, Mouth Neoplasms, Oral Squamous Cell Carcinoma, Warburg Effect, Purinergic Signaling , Mitochondria
- Abstract
-
Introduction: Oral cancer is a malignant neoplasm due to the carcinogenesis process. In this, tumor cells show a deregulation and reprogramming of cellular energy metabolism because production and proliferation of biomass is necessary. Adenosine 5-triphosphate (ATP) represents the currency of energy exchange, an extracellular key signaling molecule to mediate multiple cellular responses. Most metabolic energy originates from oxidation-reduction (redox) reactions in mitochondria, and this organelle could be affected by some of the known risk factors of developing oral cancer such as the intake of alcohol and tobacco. Therefore, ATP is proposed as a prognostic malignant transformation marker and predictive in the progress of cancer.
Methodology: Fifteen tissues from oral normal gingiva (controls) and fifteen from oral squamous cell carcinomas (OSCC) were collected. Risk habits were taken and recorded as presence or absence. OSCC clinical stages were taken from medical history, and these were evaluated according to AJCC. ATP was quantified with a luminescence-based (luciferin–luciferase) detection assay. Categorical variables were presented as frequencies and percentages, numerical variables as medians. The Mann-Whitney U non-parametric test was used for statistical analysis.
Results: Control group had the highest frequency of not consuming tobacco (n=11, 73.3%). OSCC groups showed a higher frequency of tumor with no invasion of close anatomic sites (<4cm) (n=9, 60%), no clear predilection between presence (n=8, 53.3%) and absence (n=7, 46.7%) of lymph node invasion and despite only one patient reported distant metastases, the more prevalent recorded clinical staging was the advanced stage (n=9, 60%). Smoking cigarettes showed significant influence (p <0.01) to generate higher levels of ATP (median 1.4 µM/µL) compared to non-smokers (median= 0.5 µM/µL), contrary to the group of OSCC cases. ATP concentration was significantly (p<0.001) higher in the case group (median= 1.6 µM/µL) than the control group (median= 0.9 µM/µL). The results involving the aggressiveness of the disease did not show statistical difference.
Conclusions: According to this study, in non-malignant oral tissue ATP levels could be influenced by tobacco smoke but apparently this is not applied to OSCC and independently of risk habits ATP levels could be more concentrated in oral malignant tissues increasing the levels of ATP.
- Downloads
-
Download data is not yet available.
- Author Biographies
- References
-
[1] Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6): 394-424.
https://doi.org/10.3322/caac.21492
[2] Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE, Grandis JR. Head and neck squamous cell carcinoma. Nat Rev Dis Primers. 2020; 6(1): 92.
https://doi.org/10.1038/s41572-020-00224-3
[3] Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011; 144(5): 646-74.
https://doi.org/10.1016/j.cell.2011.02.013
[4] DeBerardinis RJ, Chandel NS. Fundamentals of cancer metabolism. Sci Adv. 2016; 2(5): e1600200.
https://doi.org/10.1126/sciadv.1600200
[5] Burnstock G. Purinergic signalling. Br J Pharmacol. 2006; 147(Suppl 1): S172-81.
https://doi.org/10.1038/sj.bjp.0706429
[6] Kudryavtseva AV, Krasnov GS, Dmitriev AA, Alekseev BY, Kardymon OL, Sadritdinova AF, et al. Mitochondrial dysfunction and oxidative stress in aging and cancer. Oncotarget. 2016; 7(29): 44879-905.
https://doi.org/10.18632/oncotarget.9821
[7] Caliri AW, Tommasi S, Besaratinia A. Relationships among smoking, oxidative stress, inflammation, macromolecular damage, and cancer. Mutat Res Rev Mutat Res. 2021; 787: 108365.
https://doi.org/10.1016/j.mrrev.2021.108365
[8] Van der Toorn M, Slebos DJ, de Bruin HG, Leuvenink HG, Bakker SJL, Gans ROB, et al. Cigarette smoke-induced blockade of the mitochondrial respiratory chain switches lung epithelial cell apoptosis into necrosis. Am J Physiol Lung Cell Mol Physiol. 2007; 292(5): L1211-8.
https://doi.org/10.1152/ajplung.00291.2006
[9] Manzo-Avalos S, Saavedra-Molina A. Cellular and mitochondrial effects of alcohol consumption. Int J Environ Res Public Health. 2010; 7(12): 4281-304.
https://doi.org/10.3390/ijerph7124281
[10] Cederbaum AI. Alcohol metabolism. Clin Liver Dis. 2012; 16(4): 667-85.
https://doi.org/10.1016/j.cld.2012.08.002
[11] Liberti MV, Locasale JW. The Warburg effect: how does it benefit cancer cells? Trends Biochem Sci. 2016; 41(3): 211-8.
https://doi.org/10.1016/j.tibs.2015.12.001
[12] Corbet C, Feron O. Tumour acidosis: from the passenger to the driver's seat. Nat Rev Cancer. 2017; 17(10): 577-93.
https://doi.org/10.1038/nrc.2017.77
[13] Peng M, Yin N, Chhangawala S, Xu K, Leslie CS, Li MO. Aerobic glycolysis promotes T helper 1 cell differentiation through an epigenetic mechanism. Science. 2016; 354(6311): 481-4.
https://doi.org/10.1126/science.aaf6284
[14] Beis I, Newsholme EA. The contents of adenine nucleotides, phosphagens and some glycolytic intermediates in resting muscles from vertebrates and invertebrates. Biochem J. 1975; 152(1): 23-32.
https://doi.org/10.1042/bj1520023
[15] Hernandez-Munoz R, Glender W, Diaz-Munoz M, Suarez J, Lozano J, Chagoya de Sanchez V. Alterations of ATP levels and of energy parameters in the blood of alcoholic and nonalcoholic patients with liver damage. Alcohol Clin Exp Res. 1991; 15(3): 500-3.
https://doi.org/10.1111/j.1530-0277.1991.tb00550.x
[16] Singh MP, Kumar V, Agarwal A, Kumar R, Bhatt MLB, Misra S. Clinico-epidemiological study of oral squamous cell carcinoma: A tertiary care centre study in North India. J Oral Biol Craniofac Res. 2016; 6(1): 31-4.
https://doi.org/10.1016/j.jobcr.2015.11.002
[17] Wang Y, Jing Y, Ding L, Zhang X, Song Y, Chen S, et al. Epiregulin reprograms cancer-associated fibroblasts and facilitates oral squamous cell carcinoma invasion via JAK2-STAT3 pathway. J Exp Clin Cancer Res. 2019; 38(1): 274.
https://doi.org/10.1186/s13046-019-1277-x
[18] Young A, Oldford C, Mailloux RJ. Lactate dehydrogenase supports lactate oxidation in mitochondria isolated from different mouse tissues. Redox Biol. 2020; 28: 101339.
https://doi.org/10.1016/j.redox.2019.101339
[19] Sun K, Tang S, Hou Y, Xi L, Chen Y, Yin J, et al. Oxidized ATM-mediated glycolysis enhancement in breast cancer-associated fibroblasts contributes to tumor invasion through lactate as metabolic coupling. EBioMedicine. 2019; 41: 370-83.
https://doi.org/10.1016/j.ebiom.2019.02.025
[20] Choi SYC, Collins CC, Gout PW, Wang Y. Cancer-generated lactic acid: a regulatory, immunosuppressive metabolite? J Pathol. 2013; 230(4): 350-5.
https://doi.org/10.1002/path.4218
[21] Ngo DC, Ververis K, Tortorella SM, Karagiannis TC. Introduction to the molecular basis of cancer metabolism and the Warburg effect. Mol Biol Rep. 2015; 42(4): 819-23.
https://doi.org/10.1007/s11033-015-3857-y
[22] Zhang X, Dong Y, Zhao M, Ding L, Yang X, Jing Y, et al. ITGB2-mediated metabolic switch in CAFs promotes OSCC proliferation by oxidation of NADH in mitochondrial oxidative phosphorylation system. Theranostics. 2020; 10(26): 12044-59.
https://doi.org/10.7150/thno.47901
[23] Zhang Z, Gao Z, Rajthala S, Sapkota D, Dongre H, Parajuli H, et al. Metabolic reprogramming of normal oral fibroblasts correlated with increased glycolytic metabolism of oral squamous cell carcinoma and precedes their activation into carcinoma associated fibroblasts. Cell Mol Life Sci. 2020; 77(6): 1115-33.
- Downloads
- Published
- 25-06-2026
- Issue
- Vol. 15 No. 2 (2026)
- Section
- Articles
- Categories
- License
-
Copyright (c) 2026 Emmanuel Mendoza, José Roberto Prieto Correa , José Alfonso Cruz Ramos , Paola Monserrat Zepeda Olmos , Juan José Soto Ávila , Sandra López Verdín

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
Similar Articles
- Juan Manuel Seoane-Romero, Pablo Ignacio Varela-Centelles, Pedro Diz-Dios, Isabel Ramos-Barbosa, Javier Fernández Feijoo, Juan Seoane, Does Tumour Biological Behaviour Influence Prognosis More than Diagnostic Delay in Oral Cancer? , Journal of Cancer Research Updates: Vol. 1 No. 1 (2012)
- Suresh Chandra Yadav, Dilip Dwivedy, Deciphering the Role of Mitochondrial Metabolic Reprogramming in the Progression of Clear Cell Renal Cell Carcinoma , Journal of Cancer Research Updates: Vol. 15 No. 2 (2026)
- Abhishek Kumar Gupta, Anand Trivedi, Single Cell RNA Sequencing Analysis of the Immune Microenvironment in Treatment Resistant Esophageal Squamous Cell Carcinoma , Journal of Cancer Research Updates: Vol. 15 No. 2 (2026)
- Deepti Sharma, Abi M. Thomas, George Koshy, Tumor Infiltrating Lymphocytes as Immunebiomarkers in Oral Cancer: An Update , Journal of Cancer Research Updates: Vol. 12 (2023)
- Karina Torres Mojica, Jorge R. Miranda Massari, Jose R. Rodriguez, Jose Olalde, Miguel Berdiel, Michael J. Gonzalez, Structured Water and Cancer: Orthomolecular Hydration Therapy , Journal of Cancer Research Updates: Vol. 12 (2023)
- Jamison Wijaya, Indrayadi Gunardi, Julvyn Julvyn, Christopher Lim, Benny Nicolas Johannis, Firstine Kelsi Hartanto, Adrianus Rajasa, Rahmi Amtha, Elizabeth Fitriana Sari, Selecting the Appropriate Oral Cancer Cell Line: Characteristic-Based Recommendations from a Systematic Review , Journal of Cancer Research Updates: Vol. 14 (2025)
- Pedro Cuevas, Javier Angulo, Adrián Cuevas-Bourdier, Guillermo Giménez-Gallego, Topical Treatment of Skin Squamous Cell Carcinoma with Potassium Dobesilate Cream , Journal of Cancer Research Updates: Vol. 1 No. 1 (2012)
- Hassan Bahrami, Majid Tafrihi, Understanding the Warburg Effect Yields New Insights into the Metabolic Control of Cancer , Journal of Cancer Research Updates: Vol. 12 (2023)
- A. Al Qahtani, J.M.P. Holly, C.M. Perks, The Role of 5' Adenosine Monophosphate-Activated Protein Kinase in the Chemo-Sensitivity and Metabolic Behaviour of Breast Cancer Cells Exposed to Hypoxia and Hyperglycaemia , Journal of Cancer Research Updates: Vol. 11 (2022)
- Abdul Rashid Lone, Shiekh Aejaz Aziz, Mohmad Hussain Mir, Sumyra K. Qadri, Arif N. Bhat, Farhana S. Bagdadi, Syed Nisar, Ulfat Ara, Case Report: Primary Squamous Cell Carcinoma of Kidney-An Unusual Malignancy , Journal of Cancer Research Updates: Vol. 2 No. 3 (2013)
You may also start an advanced similarity search for this article.
