Issue
Copyright (c) 2020 Georgina Crespo, Luis Alejandro Di Toro, Valbuena Desiree, Jose Luis Perez Vicuña, María Paula Díaz , Aida Souki, Clímaco Cano, Juan Salazar
This work is licensed under a Creative Commons Attribution 4.0 International License.
Oxidative stress and its role in cancer: a molecular perspective
Corresponding Author(s) : Luis Alejandro Di Toro
Ciencia e Innovación en Salud,
2020
Abstract
Cancer development is a product of cellular growth and proliferation caused by DNA mutations, nevertheless, other processes are able to favor tumoral progression, such as the activity of reactive oxygen species (ROS) produced within cells as a result of different metabolic reactions. Oxidative stress is defined as an imbalance between free radicals and highly reactive metabolites synthesis and the antioxidant system capacity to eliminate these molecules. In this sense, the overproduction of free radicals is a typical feature of neoplastic cells that allows the promotion of cellular processes related to survival, proliferation, invasion, and metastasis. Furthermore, underlying mechanisms involved in malignant transformation can modify the antioxidant systems in charge of ROS elimination. However, cancer has the particularity of presenting a dual behavior in which both antioxidant or prooxidant activity within tumoral cells can predominate depending on the stage of the disease. As a consequence, many therapeutic efforts have been directed into the stimulation or inhibition of oxidant and antioxidant components in the tumor microenvironment. The aim of this review is to describe the role of oxidative stress in cancer biology and its therapeutic potential.
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- Torre LA, Siegel RL, Ward EM, Jemal A. Global Cancer Incidence and Mortality Rates and Trends- An Update. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol. 2016;25(1):16–27. DOI: 10.1158/1055-9965.EPI-15-0578
- Dehghani SL, Rezaianzadeh A. Trends of incidence of colorectal cancer in Iran, 2003–2010. Rev Latinoam Hipertens [Internet]. 2019;14(2):295–300. http://saber.ucv.ve/ojs/index.php/rev_lh/article/view/16784
- 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 [Internet]. 2018;68(6):394–424. https://acsjournals.onlinelibrary.wiley.com/doi/full/10.3322/caac.21492
- Iglesias L, Pérez J, Villegas J, Bastidas A. La autotoma de muestra cervico-vaginal y la toma hecha por el ginecólogo en el diagnóstico de cáncer de cuello uterino. Aplicabilidad en los programas de pesquisa de cáncer de cuello uterino. Ciencia e Innovación en Salud [Internet]. 2018;(e59):1–12. Disponible en: http://revistas.unisimon.edu.co/index.php/innovacionsalud/article/view/3041
- Arias-Rojas M, Carreño Moreno S, Arredondo Holgín E. Incertidumbre y calidad de vida en
- cuidadores familiares de personas con cáncer en cuidado paliativo. Ciencia e Innovación en Salud
- [Internet]. 2020;(e81):184–96. DOI: 10.17081/innosa.81
- Nourazarian AR, Kangari P, Salmaninejad A. Roles of oxidative stress in the development and
- progression of breast cancer. Asian Pac J Cancer Prev APJCP. 2014;15(12):4745–51. DOI:
- 7314/apjcp.2014.15.12.4745
- Korgaonkar N, Yadav KS. Understanding the biology and advent of physics of cancer with
- perspicacity in current treatment therapy. Life Sci [Internet]. 15 de diciembre de 2019 [citado 15 de junio de 2020];239:117060. http://www.sciencedirect.com/science/article/pii/S0024320519309877
- Martínez-Martínez A, Diaz-Caballero A, Quintero-Echenique N. Malignant and premalignant lesions of the tongue, clinical and histopathological findings for their early detection. Study of two cases. Ciencia e Innovación en Salud [Internet]. 2020;(e73):59-67. DOI: 10.17081/innosa.73
- Sullivan LB, Chandel NS. Mitochondrial reactive oxygen species and cancer. Cancer Metab.
- ;2:17. DOI: 10.1186/2049-3002-2-17
- Tafani M, Sansone L, Limana F, Arcangeli T, De Santis E, Polese M, et al. The Interplay of Reactive Oxygen Species, Hypoxia, Inflammation, and Sirtuins in Cancer Initiation and Progression. Oxid Med Cell Longev. 2016;2016:3907147. DOI: 10.1155/2016/3907147
- Schumacker PT. Reactive oxygen species in cancer: a dance with the devil. Cancer Cell.
- ;27(2):156–7. DOI: 10.1016/j.ccell.2015.01.007
- Shagieva G, Domnina L, Makarevich O, Chernyak B, Skulachev V, Dugina V. Depletion of
- mitochondrial reactive oxygen species downregulates epithelial-to-mesenchymal transition in
- cervical cancer cells. Oncotarget. 2017;8(3):4901–13. DOI: 10.18632/oncotarget.13612
- González-Urbaneja I. Radicales libres: Algunas consideraciones clínicas. Gac Médica Caracas [Internet]. 2006 [citado 23 de septiembre de 2020];114(2):91–8. Disponible en:
- http://ve.scielo.org/scielo.php?script=sci_arttext&pid=S0367-47622006000200001&lng=es
- Pizzino G, Irrera N, Cucinotta M, Pallio G, Mannino F, Arcoraci V, et al. Oxidative Stress: Harms and Benefits for Human Health. Oxid Med Cell Longev. 2017;2017:8416763. DOI:
- 1155/2017/8416763
- Gorrini C, Harris IS, Mak TW. Modulation of oxidative stress as an anticancer strategy. Nat Rev Drug Discov. 2013;12(12):931–47. DOI: 10.1038/nrd4002
- Lushchak VI. Free radicals, reactive oxygen species, oxidative stress and its classification. Chem Biol Interact. 2014;224:164–75. DOI: 10.1016/j.cbi.2014.10.016
- Ohnishi S, Ma N, Thanan R, Pinlaor S, Hammam O, Murata M, et al. DNA damage in inflammationrelated carcinogenesis and cancer stem cells. Oxid Med Cell Longev. 2013;2013:387014. DOI: 10.1155/2013/387014
- Roos WP, Kaina B. DNA damage-induced cell death: from specific DNA lesions to the DNA damage response and apoptosis. Cancer Lett. 2013;332(2):237–48. DOI: 10.1016/j.canlet.2012.01.007
- Nogueira V, Hay N. Molecular pathways: reactive oxygen species homeostasis in cancer cells and implications for cancer therapy. Clin Cancer Res Off J Am Assoc Cancer Res. 2013;19(16):4309– 14. DOI: 10.1158/1078-0432.CCR-12-1424
- Schieber M, Chandel NS. ROS function in redox signaling and oxidative stress. Curr Biol CB.
- ;24(10):R453-462. DOI: 10.1016/j.cub.2014.03.034
- Gill JG, Piskounova E, Morrison SJ. Cancer, Oxidative Stress, and Metastasis. Cold Spring Harb Symp Quant Biol. 2016;81:163–75. DOI: 10.1101/sqb.2016.81.030791
- Rodic S, Vincent MD. Reactive oxygen species (ROS) are a key determinant of cancer’s metabolic phenotype. Int J Cancer. 2018;142(3):440–8. DOI: 10.1002/ijc.31069
- Wu C-A, Chao Y, Shiah S-G, Lin W-W. Nutrient deprivation induces the Warburg effect through ROS/AMPK-dependent activation of pyruvate dehydrogenase kinase. Biochim Biophys Acta. 2013;1833(5):1147–56. DOI: 10.1016/j.bbamcr.2013.01.025
- Gentric G, Mieulet V, Mechta-Grigoriou F. Heterogeneity in Cancer Metabolism: New Concepts in an Old Field. Antioxid Redox Signal. 2017;26(9):462–85. DOI: 10.1089/ars.2016.6750
- Suryani Y. In Silico Analysis of Formononetin Compound as a Breast Anti Cancer. Rev Latinoam Hipertens. 2018;13(6):579–83. http://saber.ucv.ve/ojs/index.php/rev_lh/article/view/15957
- Courtnay R, Ngo DC, Malik N, Ververis K, Tortorella SM, Karagiannis TC. Cancer metabolism and the Warburg effect: the role of HIF-1 and PI3K. Mol Biol Rep. 2015;42(4):841–51.
- Marín-Hernández A. El Factor Inducido por la Hipoxia-1 (HIF-1) y la Glucólisis en las Células
- Tumorales. REB. 2009;28(2):42–51. https://link.springer.com/article/10.1007/s11033-015-3858-x
- Xu XD, Shao SX, Jiang HP, Cao YW, Wang YH, Yang XC, et al. Warburg effect or reverse Warburg effect? A review of cancer metabolism. Oncol Res Treat. 2015;38(3):117–22. DOI:
- 1159/000375435
- Phan LM, Yeung S-CJ, Lee M-H. Cancer metabolic reprogramming: importance, main features, and potentials for precise targeted anti-cancer therapies. Cancer Biol Med. 2014;11(1):1–19. DOI: 10.7497/j.issn.2095-3941.2014.01.001
- Liberti MV, Locasale JW. The Warburg Effect: How Does it Benefit Cancer Cells? Trends Biochem Sci. 2016;41(3):211–8. DOI: 10.1016/j.tibs.2015.12.001
- Martinez-Outschoorn UE, Peiris-Pagés M, Pestell RG, Sotgia F, Lisanti MP. Cancer metabolism: at therapeutic perspective. Nat Rev Clin Oncol. 2017;14(1):11–31.
- https://www.nature.com/articles/nrclinonc.2016.60
- El Sayed SM, Mahmoud AA, El Sawy SA, Abdelaal EA, Fouad AM, Yousif RS, et al. Warburg effect increases steady-state ROS condition in cancer cells through decreasing their antioxidant capacities (anticancer effects of 3-bromopyruvate through antagonizing Warburg effect). Med Hypotheses. 2013;81(5):866–70. DOI: 10.1016/j.mehy.2013.08.024
- Ježek J, Cooper KF, Strich R. Reactive Oxygen Species and Mitochondrial Dynamics: The Yin and Yang of Mitochondrial Dysfunction and Cancer Progression. Antioxid Basel Switz. 2018;7(1). DOI: 10.3390/antiox7010013
- Pisoschi AM, Pop A. The role of antioxidants in the chemistry of oxidative stress: A review. Eur J Med Chem. 2015;97:55–74. DOI: 10.1016/j.ejmech.2015.04.040
- Camacho E, Silva J, Matos M, Garrido M, Israel A. Actividad de las enzimas antioxidantes en el riñon de la rata con preeclampsia experimental. Arch Venez Farmacol Ter. 2011;30(3):44–50.
- Kanzaki H, Wada S, Narimiya T, Yamaguchi Y, Katsumata Y, Itohiya K, et al. Pathways that
References
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Dehghani SL, Rezaianzadeh A. Trends of incidence of colorectal cancer in Iran, 2003–2010. Rev Latinoam Hipertens [Internet]. 2019;14(2):295–300. http://saber.ucv.ve/ojs/index.php/rev_lh/article/view/16784
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 [Internet]. 2018;68(6):394–424. https://acsjournals.onlinelibrary.wiley.com/doi/full/10.3322/caac.21492
Iglesias L, Pérez J, Villegas J, Bastidas A. La autotoma de muestra cervico-vaginal y la toma hecha por el ginecólogo en el diagnóstico de cáncer de cuello uterino. Aplicabilidad en los programas de pesquisa de cáncer de cuello uterino. Ciencia e Innovación en Salud [Internet]. 2018;(e59):1–12. Disponible en: http://revistas.unisimon.edu.co/index.php/innovacionsalud/article/view/3041
Arias-Rojas M, Carreño Moreno S, Arredondo Holgín E. Incertidumbre y calidad de vida en
cuidadores familiares de personas con cáncer en cuidado paliativo. Ciencia e Innovación en Salud
[Internet]. 2020;(e81):184–96. DOI: 10.17081/innosa.81
Nourazarian AR, Kangari P, Salmaninejad A. Roles of oxidative stress in the development and
progression of breast cancer. Asian Pac J Cancer Prev APJCP. 2014;15(12):4745–51. DOI:
7314/apjcp.2014.15.12.4745
Korgaonkar N, Yadav KS. Understanding the biology and advent of physics of cancer with
perspicacity in current treatment therapy. Life Sci [Internet]. 15 de diciembre de 2019 [citado 15 de junio de 2020];239:117060. http://www.sciencedirect.com/science/article/pii/S0024320519309877
Martínez-Martínez A, Diaz-Caballero A, Quintero-Echenique N. Malignant and premalignant lesions of the tongue, clinical and histopathological findings for their early detection. Study of two cases. Ciencia e Innovación en Salud [Internet]. 2020;(e73):59-67. DOI: 10.17081/innosa.73
Sullivan LB, Chandel NS. Mitochondrial reactive oxygen species and cancer. Cancer Metab.
;2:17. DOI: 10.1186/2049-3002-2-17
Tafani M, Sansone L, Limana F, Arcangeli T, De Santis E, Polese M, et al. The Interplay of Reactive Oxygen Species, Hypoxia, Inflammation, and Sirtuins in Cancer Initiation and Progression. Oxid Med Cell Longev. 2016;2016:3907147. DOI: 10.1155/2016/3907147
Schumacker PT. Reactive oxygen species in cancer: a dance with the devil. Cancer Cell.
;27(2):156–7. DOI: 10.1016/j.ccell.2015.01.007
Shagieva G, Domnina L, Makarevich O, Chernyak B, Skulachev V, Dugina V. Depletion of
mitochondrial reactive oxygen species downregulates epithelial-to-mesenchymal transition in
cervical cancer cells. Oncotarget. 2017;8(3):4901–13. DOI: 10.18632/oncotarget.13612
González-Urbaneja I. Radicales libres: Algunas consideraciones clínicas. Gac Médica Caracas [Internet]. 2006 [citado 23 de septiembre de 2020];114(2):91–8. Disponible en:
http://ve.scielo.org/scielo.php?script=sci_arttext&pid=S0367-47622006000200001&lng=es
Pizzino G, Irrera N, Cucinotta M, Pallio G, Mannino F, Arcoraci V, et al. Oxidative Stress: Harms and Benefits for Human Health. Oxid Med Cell Longev. 2017;2017:8416763. DOI:
1155/2017/8416763
Gorrini C, Harris IS, Mak TW. Modulation of oxidative stress as an anticancer strategy. Nat Rev Drug Discov. 2013;12(12):931–47. DOI: 10.1038/nrd4002
Lushchak VI. Free radicals, reactive oxygen species, oxidative stress and its classification. Chem Biol Interact. 2014;224:164–75. DOI: 10.1016/j.cbi.2014.10.016
Ohnishi S, Ma N, Thanan R, Pinlaor S, Hammam O, Murata M, et al. DNA damage in inflammationrelated carcinogenesis and cancer stem cells. Oxid Med Cell Longev. 2013;2013:387014. DOI: 10.1155/2013/387014
Roos WP, Kaina B. DNA damage-induced cell death: from specific DNA lesions to the DNA damage response and apoptosis. Cancer Lett. 2013;332(2):237–48. DOI: 10.1016/j.canlet.2012.01.007
Nogueira V, Hay N. Molecular pathways: reactive oxygen species homeostasis in cancer cells and implications for cancer therapy. Clin Cancer Res Off J Am Assoc Cancer Res. 2013;19(16):4309– 14. DOI: 10.1158/1078-0432.CCR-12-1424
Schieber M, Chandel NS. ROS function in redox signaling and oxidative stress. Curr Biol CB.
;24(10):R453-462. DOI: 10.1016/j.cub.2014.03.034
Gill JG, Piskounova E, Morrison SJ. Cancer, Oxidative Stress, and Metastasis. Cold Spring Harb Symp Quant Biol. 2016;81:163–75. DOI: 10.1101/sqb.2016.81.030791
Rodic S, Vincent MD. Reactive oxygen species (ROS) are a key determinant of cancer’s metabolic phenotype. Int J Cancer. 2018;142(3):440–8. DOI: 10.1002/ijc.31069
Wu C-A, Chao Y, Shiah S-G, Lin W-W. Nutrient deprivation induces the Warburg effect through ROS/AMPK-dependent activation of pyruvate dehydrogenase kinase. Biochim Biophys Acta. 2013;1833(5):1147–56. DOI: 10.1016/j.bbamcr.2013.01.025
Gentric G, Mieulet V, Mechta-Grigoriou F. Heterogeneity in Cancer Metabolism: New Concepts in an Old Field. Antioxid Redox Signal. 2017;26(9):462–85. DOI: 10.1089/ars.2016.6750
Suryani Y. In Silico Analysis of Formononetin Compound as a Breast Anti Cancer. Rev Latinoam Hipertens. 2018;13(6):579–83. http://saber.ucv.ve/ojs/index.php/rev_lh/article/view/15957
Courtnay R, Ngo DC, Malik N, Ververis K, Tortorella SM, Karagiannis TC. Cancer metabolism and the Warburg effect: the role of HIF-1 and PI3K. Mol Biol Rep. 2015;42(4):841–51.
Marín-Hernández A. El Factor Inducido por la Hipoxia-1 (HIF-1) y la Glucólisis en las Células
Tumorales. REB. 2009;28(2):42–51. https://link.springer.com/article/10.1007/s11033-015-3858-x
Xu XD, Shao SX, Jiang HP, Cao YW, Wang YH, Yang XC, et al. Warburg effect or reverse Warburg effect? A review of cancer metabolism. Oncol Res Treat. 2015;38(3):117–22. DOI:
1159/000375435
Phan LM, Yeung S-CJ, Lee M-H. Cancer metabolic reprogramming: importance, main features, and potentials for precise targeted anti-cancer therapies. Cancer Biol Med. 2014;11(1):1–19. DOI: 10.7497/j.issn.2095-3941.2014.01.001
Liberti MV, Locasale JW. The Warburg Effect: How Does it Benefit Cancer Cells? Trends Biochem Sci. 2016;41(3):211–8. DOI: 10.1016/j.tibs.2015.12.001
Martinez-Outschoorn UE, Peiris-Pagés M, Pestell RG, Sotgia F, Lisanti MP. Cancer metabolism: at therapeutic perspective. Nat Rev Clin Oncol. 2017;14(1):11–31.
https://www.nature.com/articles/nrclinonc.2016.60
El Sayed SM, Mahmoud AA, El Sawy SA, Abdelaal EA, Fouad AM, Yousif RS, et al. Warburg effect increases steady-state ROS condition in cancer cells through decreasing their antioxidant capacities (anticancer effects of 3-bromopyruvate through antagonizing Warburg effect). Med Hypotheses. 2013;81(5):866–70. DOI: 10.1016/j.mehy.2013.08.024
Ježek J, Cooper KF, Strich R. Reactive Oxygen Species and Mitochondrial Dynamics: The Yin and Yang of Mitochondrial Dysfunction and Cancer Progression. Antioxid Basel Switz. 2018;7(1). DOI: 10.3390/antiox7010013
Pisoschi AM, Pop A. The role of antioxidants in the chemistry of oxidative stress: A review. Eur J Med Chem. 2015;97:55–74. DOI: 10.1016/j.ejmech.2015.04.040
Camacho E, Silva J, Matos M, Garrido M, Israel A. Actividad de las enzimas antioxidantes en el riñon de la rata con preeclampsia experimental. Arch Venez Farmacol Ter. 2011;30(3):44–50.
Kanzaki H, Wada S, Narimiya T, Yamaguchi Y, Katsumata Y, Itohiya K, et al. Pathways that