Skip to main content
SpringerLink
Log in

Glutathione as Oxidative Stress Marker in Cancer

  • Living reference work entry
  • First Online:
Handbook of Oxidative Stress in Cancer: Mechanistic Aspects

Abstract

In this review I describe the novel effect of glutathione (GSH) as an oxidative stress marker in cancer based on the recent research findings. Each and every living organism’s cell has its own antioxidant capacity to control them, if any condition that forces to cross the antioxidant capacity of the cell may denature the proteins, lipids, and finally spoil the cells. These oxidative stresses could be caused due to either increase in the level of reactive oxygen species (ROS) or impairment of the antioxidant defense system. Predominantly glutathione helps to preserve the antioxidant defense in the body thereby detoxifying chemicals, including some that our body creates naturally, as well as pollutants and drugs. 

GSH has sulfhydryl rich group of six potential coordination sites for binding and two peptide bonds for metal cations. The secret power for GSH is sponsored by the richest non-protein thiols of mammalian cells that act as a reducing agent and as a major antioxidant within cells. The toxic peroxide groups are converted to nontoxic hydroxyl groups by catalyzing during the conversion to GSSG from GSH. That helps the breakdown of H2O2 to protect the membrane from injuring caused by peroxide.

Metals have an affinity with GSH to bind. Altered level of GSH has a role in programmed cell death involving the degradation of cellular constituent (apoptosis) and consumption of the body’s own tissue as a metabolic process occurring in starvation and certain diseases (autophagy). GSH reduction can occur in both (intrinsic) mitochondrial-mediated apoptosis and (extrinsic) death receptor-mediated apoptosis based on tumorigenesis by two possible mechanisms: gene mutation and transcription factors (TF).

Oxidative stress is notorious for modifying signaling pathways, spoil the DNA molecule, and control progression of different cancers, including breast, ovary, colon, lung, liver, brain, and prostate cancers. Glutathione homeostasis is also essential to many processes, including immune response, reactivation of other antioxidants and metabolism of medications, toxins, radiation and carcinogens. Glutathione has a notable alteration in various cancer cells present in body organs with different correlations and parameters, and the glutathione has shown predominant changes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Abdalla MY (2011) Glutathione as potential target for cancer therapy; more or less is good? Jordan J Biol Sci 4:119–124

    Google Scholar 

  • Alanazi AM, Mostafa G, Al-Badr AA (2015) Glutathione. Prof Drug Substan Excip Rel Methodol 40:43–158

    Article  CAS  Google Scholar 

  • Almondes KG d S, Leal GV d S, Cozzolino SMF, Philippi ST, Rond PH d C (2010) The role of selenoproteins in cancer. Rev Assoc Med Bras 56:484–4848

    Article  PubMed  Google Scholar 

  • Anderton B, Camarda R, Balakrishnan S, Balakrishnan A, Kohnz RA, Lim L, Evason KJ, Momcilovic O, Kruttwig K, Huang Q, Xu G, Nomura DK, Goga A (2017) MYC-driven inhibition of the glutamate-cysteine ligase promotes glutathione depletion in liver cancer. EMBO Rep 18:569–585

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Angel LO, Mena S, Estrela JM (2011) Glutathione in cancer cell death. Cancers 3:1285–1310

    Article  Google Scholar 

  • Ankita B, Celeste Simon M (2018) Glutathione metabolism in cancer progression and treatment resistance. J Cell Biol 217:2291–2298

    Article  Google Scholar 

  • Baltruskeviciene E, Kazbariene B, Badaras R, Bagdonait L, Krikštaponien A, Zdanavicius L, Aleknavicius E, Didziapetrien J (2016) Glutathione and glutathione S-transferase levels in patients with liver metastases of colorectal cancer and other hepatic disorders. Turk J Gastroenterol 27(4):336–341

    Article  PubMed  Google Scholar 

  • Bansal A, Simon MC (2018) Glutathione metabolism in cancer progression and treatment resistance. J Cell Biol 217:2291–2298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Benedette C (2018) Foods that reduce oxidative stress and prevent cancer. Available via https://www.news-medical.net/health/Foods-that-Reduce-Oxidative-Stress-and-Prevent-Cancer.aspx. Accessed 15 Jan 2020:1–6

  • Cacciatore I, Cornacchia C, Pinnen F, Mollica A, Di Stefano A (2010) Prodrug approach for increasing cellular glutathione levels. Molecules 15:1242–1264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Canli GAM (2008) Responses of metallothionein and reduced glutathione in a freshwater fish Oreochromis niloticus following metal exposures. Environ Toxicol Pharmacol 25:33–38

    Article  PubMed  Google Scholar 

  • Chakravarthi S, Jessop CE, Bulleid NJ (2006) The role of glutathione in disulphide bond formation and endoplasmic-reticulum-generated oxidative stress. Eur Mol Biol Organ 7:270–275

    Google Scholar 

  • Cheves T. Walling (2018) Radical. Encyclopedia Britannica. https://www.britannica.com/science/radical-chemistry. Access on02 March 2020

  • Deanna M. Minich, Benjamin I. Brown (2019) A Review of Dietary (Phyto)Nutrients for Glutathione Support. Nutrients 11:1–20

    Google Scholar 

  • Deng J, Liu A-D, Hou G-Q, Zhang X, Ren K, Chen X-Z, Li SSC, Wu Y-S, Cao X (2019) N-acetylcysteine decreases malignant characteristics of glioblastoma cells by inhibiting Notch2 signaling. J Exp Clin Cancer Res 38:1–15

    Article  CAS  Google Scholar 

  • Di Matteo A, Federici L, Masulli M, Carletti E, Santorelli D, Cassidy J, Paradisi F, Di Ilio C, Allocat N (2019) Structural characterization of the Xi class glutathione transferase from the haloalkaliphilic archaeon Natrialba magadii. Front Microbiol 10:1–12

    Article  Google Scholar 

  • Du ZX, Zhang HY, Meng X, Guan Y, Wang HQ (2009) Role of oxidative stress and intracellular glutathione in the sensitivity to apoptosis induced by proteasome inhibitor in thyroid cancer cells. BMC Cancer 16:1–11

    Google Scholar 

  • Edie summers (2016) The memory of health. Media high 257

    Google Scholar 

  • Forman HJ, Zhang H, Rinna A (2009) Glutathione: Overview of its protective roles, measurement, and biosynthesis. Mol Asp Med 30:1–12

    Article  CAS  Google Scholar 

  • Gallant KR, Cherian MG (1989) Metabolic changes in glutathione and metallothionein in newborn rat liver. J Pharmacol Exp Ther 249(2):631–637

    CAS  PubMed  Google Scholar 

  • Gard-Genetic and rare disease information centre. Glutathione synthetase deficiency. https://rarediseases.info.nih.gov/diseases/10047/glutathione-synthetase-deficiency. Accessed 29 Feb 2020

  • Guluzar Atli Mustafa Canli (2008) Responses of metallothionein and reduced glutathione in a freshwater fish Oreochromis niloticus following metal exposures. Envi toxicology and pharmacology 25:33–38

    Google Scholar 

  • Hasanuzzaman M, Nahar K, Anee TI, Fujita M (2017) Glutathione in plants: biosynthesis and physiological role in environmental stress tolerance. Physiol Mol Biol Plants 23(2):249–268

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hodges RE, Minich DM (2015) Modulation of metabolic detoxification pathways using foods and food-derived components: a scientific review with clinical application. J Nutr Metab 760689:1–23

    Article  Google Scholar 

  • Huanhuan LV, Chenxiao Zhen, Junyu Liu, Pengfei Yang, Lijiang Hu, Peng Shang (2019) Unraveling the potential role of glutathione in multiple forms of cell death in cancer therapy. Oxidative Medicine and Cellular Longevity 3150145:1–16

    Google Scholar 

  • Ie Ming Shih, Ben Davidson (2009) Pathogenesis of ovarian cancer: clues from selected overexpressed genes. Future Oncol 5(10):1–23

    Google Scholar 

  • Irie M, Sohda T, Anan A, Fukunaga A, Takata K, Tanaka T, Yokoyama K, Morihara D, Takeyama Y, Shakado S, Sakisaka S (2016) Reduced glutathione suppresses oxidative stress in nonalcoholic fatty liver disease. Eur J Hep Gastroenterol 6:13–18

    Google Scholar 

  • Joseph Pizzorno ND (2014) Glutathione. Integ Med 13:8–15

    Google Scholar 

  • Katakwar P, Metgud R, Naik S, Mittal R (2016) Oxidative stress marker in oral cancer: a review. J Cancer Res Ther 12:438–446

    Article  CAS  PubMed  Google Scholar 

  • Ke H-L, Lin J, Ye Y, Wu W-J, Lin H-H, Wei H, Huang M, Chang DW, Dinney CP, Wu X (2015) Genetic variations in glutathione pathway genes predict cancer recurrence in patients treated with transurethral resection and Bacillus Calmette-Guerin instillation for non-muscle invasive bladder cancer. Ann Surg Oncol 22:4104–4110

    Article  PubMed  PubMed Central  Google Scholar 

  • Kerksick C, Willoughby D (2005) The antioxidant role of glutathione and N-acetylcysteine supplements and exercise-induced oxidative stress. J Int Soc Sports Nutr 2(2):38–44

    Article  PubMed  PubMed Central  Google Scholar 

  • Kaluce Goncalves de Sousa Almondes, Greisse Viero da Silva Leal, Silvia Maria Franciscato Cozzolino, Sonia Tucunduva Philippi, Patrícia Helen de Carvalho Rond (2010) The role of selenoproteins in cancer. Rev Assoc Med Bras 56:484–518

    Google Scholar 

  • Kathryn E. Wellen and Craig B. Thompson (2010) Cellular Metabolic Stress: Considering How Cells Respond to Nutrient Excess. Mol Cell 40:323–332

    Google Scholar 

  • Kumari S, Badana AK, Murali Mohan G, Shailender G, Malla RR (2018) Reactive oxygen species: a key constituent in cancer survival. Biomark Insights 13:1–9

    Article  Google Scholar 

  • Kurutas EB (2016) The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state. Kurutas Nutr J 15:1–22

    Google Scholar 

  • Laua A, Villeneuvea NF, Suna Z, Wong b PK, Zhang DD (2008) Dual roles of Nrf2 in cancer. Pharmacol Res 58:262–270

    Article  Google Scholar 

  • Lushchak VI (2012) Glutathione homeostasis and functions: potential targets for medical interventions. J Amino Acid 10(1125):1–26

    Google Scholar 

  • Lv H, Zhen C, Liu J, Yang P, Hu L, Shang P (2019) Unraveling the potential role of glutathione in multiple forms of cell death in cancer therapy. Oxidative Med Cell Longev 3150145:1–16

    Google Scholar 

  • Maher Y. Abdalla (2011) Glutathione as potential target for cancer therapy; more or less is good? Jordan J Bio Sci 4:119–124

    Google Scholar 

  • Malgorzata Nita, Andrzej Grzybowski (2016) The role of the reactive oxygen species and oxidative stress in the pathomechanism of the age-related ocular diseases and other pathologies of the anterior and posterior eye segments in adults. Oxidative Medicine and Cellular Longevity 3164734:1–23

    Google Scholar 

  • Melinda Wenner M (2015) Antioxidants may make cancer worse. Scientific American. Available via https://www.scientificamerican.com/article/antioxidants-may-make-cancer-worse/. Accessed 15 Jan 2020

  • Mayne ST (2013) Oxidative stress, dietary antioxidant supplements, and health:is the glass half full or half empty? Cancer Epidemiol Biomark Prev 22:2145–2147

    Article  Google Scholar 

  • Minich DM, Brown BI (2019) A review of dietary (phyto)nutrients for glutathione support. Nutrients 11:1–20

    Article  Google Scholar 

  • Morris G, Anderson G, Dean O, Berk M, Galecki P, Martin-Subero M, Maes M (2014) The glutathione system: a new drug target in neuroimmune disorders. Mol Neurobiol 50:1059–1084

    Article  CAS  PubMed  Google Scholar 

  • Nita M, Grzybowski A (2016) The role of the reactive oxygen species and oxidative stress in the pathomechanism of the age-related ocular diseases and other pathologies of the anterior and posterior eye segments in adults. Oxidative Med Cell Longev 3164734:1–23

    Article  Google Scholar 

  • Noctor G, Queval G, Mhamdi A, Chaouch S, Foyer CH (2011) Glutathione. Am Soc Plant Biol 142:1–32

    Google Scholar 

  • Noda N, Wakasugi H (2001) Cancer and oxidative stress. J Jpn Med Assoc 44(535–539):2001

    Google Scholar 

  • Panieri E, Saso L (2019) Potential applications of NRF2 inhibitors in cancer therapy. Oxidative Med Cell Longev 8592348:1–34

    Article  Google Scholar 

  • Pfister C, Dawzcynski H, Schingale F-J (2016) Sodium selenite and cancer related lymphedema: biological and pharmacological effects. J Trace Elem Med Biol 37:111–116

    Article  CAS  PubMed  Google Scholar 

  • Matthew P-H (2016) Your body’s detoxification pathways. The great plains laboratory, Inc Available via https://www.greatplainslaboratory.com/gpl-blog-source/2016/6/6/your-bodys-detoxification-pathways. Accessed 15 Jan

  • Payal Katakwar, Rashmi Metgud, Smitha Naik, Rashu Mittal (2016) Oxidative stress marker in oral cancer: A review. J Can Res Ther 12:438–446

    Google Scholar 

  • Phaniendra A, Jestadi DB, Periyasamy L (2015) Free radicals: properties, sources, targets, and their implication in various diseases. Indian J Clin Biochem 30(1):11–26

    Article  CAS  PubMed  Google Scholar 

  • Romilly E. Hodges, Deanna M. Minich (2015) Modulation of Metabolic Detoxification Pathways Using Foods and Food-Derived Components: A Scientific Review with Clinical Application. J Nutr Metab 760689:1–23

    Google Scholar 

  • Saha SK, Lee SB, Won J, Choi HY, Kim K, Yang G-M, Dayem AA, Cho S-g (2017) Correlation between oxidative stress, nutrition, and cancer initiation. Int J Mol Sci 18:1–30

    Article  Google Scholar 

  • Sharma P, Jha AB, Dubey RS, Pessarakli M (2012) Reactive oxygen species, oxidative damage, and antioxidative defense mechanism in plants under stressful conditions. J Bot 217037:1–26

    Google Scholar 

  • Shih IM, Davidson B (2009) Pathogenesis of ovarian cancer: clues from selected overexpressed genes. Future Oncol 5(10):1–23

    Article  Google Scholar 

  • Sznarkowska A, Kostecka A, Meller K, Bielawski KP (2017) Inhibition of cancer antioxidant defense by natural compounds. Oncotarget 8:15996–16016

    Article  PubMed  Google Scholar 

  • Dwayne T, Melisa A, Fabian M, Kurt V, Lennox A-J, Donovan Mc G (2019) Dietary antioxidants in the chemoprevention of prostate cancer. Available via https://doi.org/10.5772/intechopen.85770. Accessed 17 Jan 2020:1–25

  • Thirumoorthy N, Manisenthil Kumar KT, Shyam Sundar A, Panayappan L, Chatterjee M (2007) Metallothionein: an overview. W J Gastroenterol 21:993–996

    Article  Google Scholar 

  • Thirumoorthy N, Shyam Sunder A, Manisenthil Kumar KT, Senthil kumar M, Ganesh Malay Chatterjee GNK (2011) A review of metallothionein isoforms and their role in pathophysiology. World J Surg Oncol 54:2–7

    Google Scholar 

  • Tokumoto M, Lee J-Y, Shimada A, Tohyama C, Satoh M (2018) Glutathione has a more important role than metallothionein-I/II against inorganic mercury-induced acute renal toxicity. J Toxicol Sci 43:275–280

    Article  CAS  PubMed  Google Scholar 

  • Traverso N, Ricciarelli R, Marengo B, Furfaro AL (2014) Role of glutathione in cancer progression and chemoresistance. Oxid Med Cell Longev 10:1–10

    Google Scholar 

  • Volodymyr I. Lushchak (2012) Glutathione homeostasis and functions: potential targets for medical interventions. J of Amino Acids 10:1125:1–26

    Google Scholar 

  • Walling CT (2018) Radical. Encyclopaedia Britannica https://www.britannica.com/science/radical-chemistry. Accessed on 02 Mar 2020

  • Wellen KE, Thompson CB (2010) Cellular metabolic stress: considering how cells respond to nutrient excess. Mol Cell 40:323–332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zalups RK, Bridges CC (2010) Renal handling and toxicity of mercury. Compr Toxicol (Second Edition) 7:475–493

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Caritas College of Pharmacy, Caritas Educity, Kottayam, Kerala, India

    N. Thirumoorthy

  2. Medex Healthcare Group, Dubai, UAE

    R. Senthilkumaran

  3. St.James College of Pharmacy, Chalakudi, Kerala, India

    L. Panayappan

  4. Ultra College of Pharmacy, Madurai, Tamilnadu, India

    Babu Thandapani

  5. Sree Abirami College of Pharmacy, Coimbatore, Tamilnadu, India

    K. Ranganathan

Authors
  1. N. Thirumoorthy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Senthilkumaran
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. Panayappan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Babu Thandapani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K. Ranganathan
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Biochemistry and Biophysic, University of Kalyani Department of Biochemistry and Biophysic, Kalyani, West Bengal, India

    Sajal Chakraborti

  2. Dept of Veterinary Pathobiology, University of Missouri, College Vet, Columbia, MO, USA

    Bimal K Ray

  3. Saroj Gupta Cancer Centre & Research Ins, Kolkata, India

    Sushanta Roychowdhury

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Singapore Pte Ltd.

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Thirumoorthy, N., Senthilkumaran, R., Panayappan, L., Thandapani, B., Ranganathan, K. (2021). Glutathione as Oxidative Stress Marker in Cancer. In: Chakraborti, S., Ray, B.K., Roychowdhury, S. (eds) Handbook of Oxidative Stress in Cancer: Mechanistic Aspects. Springer, Singapore. https://doi.org/10.1007/978-981-15-4501-6_29-1

Download citation

  • DOI: https://doi.org/10.1007/978-981-15-4501-6_29-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-15-4501-6

  • Online ISBN: 978-981-15-4501-6

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics

Search

Navigation