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Antioxidants: Cancer’s Friend or Foe?


Antioxidants

There is a delicate balance between oxidants and antioxidants in health and disease. In most cases, free radicals may contribute to disease onset and/or progression but may also play a key role in disease prevention. In this article, I will share some of the pros and cons of antioxidants in cancer progression and treatment according to research.


Antioxidants are known to be important in terms of their ability to protect against cell damage by decreasing reactive oxygen species (ROS) levels. There are so many different antioxidants, some we have never even heard of yet. Common examples are Vitamin C, Vitamin E, Lipoic Acid and Glutathione (GSH).


Glutathione is often referred to as the master antioxidant because it is said to be found in nearly every single cell in the body. It may even improve the activity of other antioxidants such as vitamin C and E according to some study.


In cancer, elevated rates of ROS have been detected in almost all types though, it plays a dual role. Because of these, antioxidants play both protective and pathogenic roles as well in cancer.


Antioxidants help all cells, including Cancer cells.


In healthy cells, antioxidants are crucial for the removal and detoxification of carcinogens and alterations in this pathway can have a profound effect on cell survival. However, elevated antioxidants levels in tumor cells are associated with tumor progression and increased resistance to chemotherapeutic drugs.


According to laboratory research, GSH has been shown to protect cells against reactive oxygen species and reactive nitrogen species. This proves true even to tumor cells. A large percentage of tumor cells with high GSH content were able to survive in the presence of the nitrosative and oxidative stress as per study.


Another study with extended follow-up of participants shows that healthy men with average risk of prostate cancer who took a common dose and formulation of vitamin E (400 IU/d) have a significantly increased risk of prostate cancer.


Antioxidants help in Cancer Treatment


Recently, several novel therapies have been developed to target the GSH antioxidant system in tumors as a means for increased response and decreased drug resistance.


Enhancing the capacity of antioxidants, in order to protect cells from redox-related changes, still persists as aim in the search for cytoprotective strategies against cancer.


On the contrary, the strategy of depleting GSH and related detoxification pathways is aimed at making cancer cells vulnerable to chemotherapy, the so-called chemosensitization.


Antioxidants help Prevent Cisplatin (CDDP)-induced Toxicity


GSH-based medication has also been successfully employed to protect against cisplatin (CDDP) induced toxicity.


One study with 50 patients having advanced gastric cancer treated with a weekly CDDP-based regimen provided evidence that GSH is a promising and effective new drug for the prevention of CDDP-induced neuropathy. It does not reduce the clinical activity of chemotherapeutic drugs.


Another study with 151 patients suffering from ovarian cancer (stage I-IV) demonstrated that adding GSH to CDDP allows more cycles of CDDP treatment to be administered because less toxicity is observed and the patient's quality of life is improved. There was a statistically significant improvement in depression, emesis, peripheral neurotoxicity, hair loss, shortness of breath and difficulty concentrating. As an indication of overall activity, these patients were statistically significantly more able to undertake housekeeping and shopping.



Healthy diet

Summary


In conclusion, there are certainly benefits in the use of antioxidants, such as glutathione, for cancer patients though, a certain balance is needed. It protects against DNA damage and demonstrates a protective role against carcinogens on noncancerous tissues. However, by conferring resistance to a number of chemotherapeutic drugs, elevated levels of glutathione in tumour cells are able to protect cancer cells as well.


The modulation of antioxidants is a double-edged sword, both sides of which have been exploited for potential therapeutic benefits. Current guidelines should be followed before supplementing antioxidants during cytotoxic treatment.


Reference:


Ballatori N, Krance SM, Notenboom S, Shi S, Tieu K, Hammond CL. Glutathione dysregulation and the etiology and progression of human diseases. Biol Chem. 2009;390(3):191-214.19166318


Carretero, J., Obrador, E., Esteve, J. M., Ortega, A., Pellicer, J. A., Sempere, F. V., & Estrela, J. M. (2001). Tumoricidal activity of endothelial cells. Inhibition of endothelial nitric oxide production abrogates tumor cytotoxicity induced by hepatic sinusoidal endothelium in response to B16 melanoma adhesion in vitro. The Journal of biological chemistry, 276(28), 25775–25782. https://doi.org/10.1074/jbc.M101148200


Cascinu, S., Cordella, L., Del Ferro, E., Fronzoni, M., & Catalano, G. (1995). Neuroprotective effect of reduced glutathione on cisplatin-based chemotherapy in advanced gastric cancer: a randomized double-blind placebo-controlled trial. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 13(1), 26–32. https://doi.org/10.1200/JCO.1995.13.1.26


Kennedy, L., Sandhu, J. K., Harper, M. E., & Cuperlovic-Culf, M. (2020). Role of glutathione in cancer: From mechanisms to therapies. Biomolecules, 10(10), 1429.


Klein, E. A., Thompson, I. M., Tangen, C. M., Crowley, J. J., Lucia, M. S., Goodman, P. J., ... & Baker, L. H. (2011). Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Jama, 306(14), 1549-1556.


Kuhlmann MK, Burkhardt G, Köhler H. Insights into potential cellular mechanisms of cisplatin nephrotoxicity and their clinical application. Nephrol Dial Transplant. 1997 Dec;12(12):2478-80. doi: 10.1093/ndt/12.12.2478. PMID: 9430835.


Liou, G. Y., & Storz, P. (2010). Reactive oxygen species in cancer. Free radical research, 44(5), 479–496. https://doi.org/10.3109/10715761003667554


Reczek, C. R., & Chandel, N. S. (2017). The two faces of reactive oxygen species in cancer. Annual Review of Cancer Biology, 1, 79-98.


Smyth, J. F., Bowman, A., Perren, T., Wilkinson, P., Prescott, R. J., Quinn, K. J., & Tedeschi, M. (1997). Glutathione reduces the toxicity and improves quality of life of women diagnosed with ovarian cancer treated with cisplatin: results of a double-blind, randomised trial. Annals of oncology : official journal of the European Society for Medical Oncology, 8(6), 569–573. https://doi.org/10.1023/a:1008211226339


Traverso, N., Ricciarelli, R., Nitti, M., Marengo, B., Furfaro, A. L., Pronzato, M. A., ... & Domenicotti, C. (2013). Role of glutathione in cancer progression and chemoresistance. Oxidative medicine and cellular longevity, 2013.


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