radiotherapy<\/strong>. It increases the apoptosis of cancerous cells selectively when used with radiotherapy. In this regard, many experiments have been performed on different tumor cell lines and animal models. Human cervical cancer cell lines (HeLa) were used to check the effect of 2-DG in combination with radiation therapy. It was found that the cancer cells were deprived of glucose 8 hours after the treatment of radiation and 2-DG. This led to the death of metastatic cells due to glucose and nutrient deprivation. It was also found that any disruption in thiol metabolism can lead to cell toxicity using thiol antioxidants like NAC. Experiments showed that the effects of 2-DG were more severe for the transformed or cancerous cells than those of normal cells.<\/span><\/p>\n <\/p>\n
2-DG can be used in combination with\u00a0L-buthionine- [S, R]-sulfoximine (BSO)<\/strong>\u00a0drug that is given to cancer patients as a therapy because it targets the\u00a0Glutamate Cysteine Ligase (GCL)<\/strong>\u00a0enzyme, which is a rate-limiting enzyme involved in the synthesis of Glutathione. Glutathione is an important enzyme protecting cells from damage caused by reactive oxygen species. When tumor cells are treated with\u00a02-DG<\/strong>\u00a0in addition to this drug, this downregulates the level of GCL enzyme in tumor cells, causing oxidative stress in the cancer cells and malignant cell death by apoptosis.<\/span><\/p>\n <\/p>\n
Cisplatin<\/span><\/strong>\u00a0can also be used in combination with glucose analog\u00a02-DG<\/strong>; it is an anti-cancerous agent being used as a drug to treat different types of cancers, especially head and neck cancer. It is used either alone or in combination with other therapies, such as anti-tumor drugs or radiotherapies. Cisplatin has different side effects, so it is not being used for clinical trials yet. Cisplatin inhibits the replication of DNA as well as the transcription of various genes involved in cell proliferation and survival, thus leading to cell death. If cisplatin is used in combination with 2-DG<\/strong>, it will not only increase the oxidative stress in cancer cells but also lead to cancer cell death. Different experiments have been performed to prove this hypothesis.\u00a0<\/span><\/p>\n <\/p>\n
2-DG is also being used in combination with different chemotherapeutic agents, these free radicals increase the production of reactive oxygen species within the cancerous cells. In breast cancer cells, it has been found that ROS causes Taxol toxicity. Taxols are used as a chemotherapeutic agent in breast cancer patients. This could be overcome when chemotherapeutic drugs are combined with 2-DG, a promising therapy for breast and lung cancer patients.<\/span><\/p>\n <\/p>\n
Different assays are used to measure the viability of cells. Experiments have shown that the cancer cells, when treated with\u00a02-DG<\/strong>, show a greater concentration of glucose transporters at the start, increasing the uptake of 2-DG binding glucose transporters. This 2-DG targets\u00a0Caspase-3<\/strong>\u00a0and Poly A Polymerase (PARP<\/strong>) enzyme, involved in inducing cell death by cleaving DNA, thus depriving cancer cells of nutrients and inducing the process of apoptosis.<\/span><\/p>\nThe effect of\u00a02-DG<\/strong>\u00a0on cancer cells can be checked using the\u00a0MTT assay<\/strong>, which determines the type of dead cells undergoing apoptosis. 2-DG mainly targets the caspases that are active enzymes playing a role in apoptosis. Usually, caspase three and\u00a0PARP<\/strong>\u00a0enzyme activity is measured to check if cells have undergone apoptosis.\u00a0PARP<\/strong>\u00a0enzyme is involved in the cleavage of DNA during the process of apoptosis. It was found through experiments that when cancer cells are treated with\u00a02-DG<\/strong>, both the Caspase 3 and the PARP activity is increased, thus increasing the process of apoptosis in these cells.\u00a0<\/span><\/p>\n <\/p>\n
The levels of\u00a0GluT-1<\/strong>\u00a0transporter protein can also be checked in cancer cells after treatment with 2-DG to study the effects of glucose analog. Experiments have shown that the transformed cells have increased levels of glucose transporter proteins as compared to the untransformed cells. Because more significant the number of glucose transporters in a cell, the more the number of\u00a02-DG<\/strong>\u00a0will bind to them, being the glucose analog. This will inhibit the binding of glucose molecules, thus depriving the cells of glucose and nutrients. When cancer cells do not have enough glucose and nutrients, they cannot proliferate rapidly, an essential hallmark of cancer cells, and hence cannot grow properly. Thus, moving toward cell death.<\/span><\/p>\n <\/p>\n
2-DG<\/span><\/strong>\u00a0has become an essential aspect of cancer therapeutics study because of its two critical properties, the inhibition of glycolysis by 2-DG and its accumulation in the cancer cells. Because of these properties, it is used as an anticancer therapeutic agent in cancer patients. When cancer cells are treated with 2-DG, they undergo a stress response at the start, which causes an increase in the number of glucose transporter proteins like\u00a0GluT1<\/strong>, causing increased movement of 2-DG into the cells decreased intake of normal glucose molecules. Thus, diminishing the glucose and nutrient concentration in these cells and inducing apoptosis.\u00a0<\/span><\/p>\nFurther, 2-DG can also be used with other anticancer therapies like radiotherapy and chemotherapy to exhibit a synergistic anticancer effect. Different assays are being used to check the results of 2-DG on cancer cells.<\/span><\/p>\n\u00a0<\/span><\/h2>\nReferences\u00a0<\/span><\/h1>\nAft, R. L., Zhang, F. W., & Gius, D. (2002). Evaluation of 2-deoxy-D-glucose as a chemotherapeutic agent: Mechanism of cell death.\u00a0British Journal of Cancer<\/em>,\u00a087<\/em>(7), 805\u2013812. https:\/\/doi.org\/10.1038\/sj.bjc.6600547<\/span><\/p>\nAiestaran-Zelaya, I., S\u00e1nchez-Guisado, M. J., Villar-Fernandez, M., Azkargorta, M., Fadon-Padilla, L., Fernandez-Pelayo, U., Perez-Rodriguez, D., Ramos-Cabrer, P., Spinazzola, A., Elortza, F., Ru\u00edz-Cabello, J., & Holt, I. J. (2022). 2 deoxy-D-glucose augments the mitochondrial respiratory chain in the heart.\u00a0Scientific Reports<\/em>,\u00a012<\/em>(1), 1\u20139. https:\/\/doi.org\/10.1038\/s41598-022-10168-1<\/span><\/p>\nJain, V. (2009).\u00a0Targeting glucose metabolism with 2-deoxy-<\/em>.\u00a05<\/em>, 581\u2013585.<\/span><\/p>\nSchwartz, D. L., Rajendran, J., Yueh, B., Coltrera, M., Anzai, Y., Krohn, K., & Eary, J. (2003). “Staging of Head and Neck Squamous Cell Cancer with Extended-Field FDG-PET.”\u00a0Archives of Otolaryngology-Head and Neck Surgery<\/em>,\u00a0129<\/em>(11), 1173\u20131178. https:\/\/doi.org\/10.1001\/archotol.129.11.1173<\/span><\/p>\nSpitz, D., Simons, A., Mattson, D., & Dornfeld, K. (2009). “Glucose deprivation-induced metabolic oxidative stress and cancer therapy.\u00a0Journal of Cancer Research and Therapeutics<\/em>,\u00a05<\/em>(9), 2. https:\/\/doi.org\/10.4103\/0973-1482.55133″<\/span><\/p>\nSwerdlow, R. H. (2009). The neurodegenerative mitochondriopathies.\u00a0Journal of Alzheimer\u2019s Disease<\/em>,\u00a017<\/em>(4), 737\u2013751. https:\/\/doi.org\/10.3233\/JAD-2009-1095<\/span><\/p>\nYao, J., Chen, S., Mao, Z., Cadenas, E., & Brinton, R. D. (2011). 2-deoxy-D-glucose treatment induces ketogenesis, sustains mitochondrial function, and reduces pathology in a female mouse model of Alzheimer\u2019s disease.\u00a0PLoS ONE<\/em>,\u00a06<\/em>(7). https:\/\/doi.org\/10.1371\/journal.pone.0021788<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"Cancer cells have some important hallmarks, one being aerobic glycolysis or increased glucose metabolism compared to normal cells. It is essential to control the glucose metabolism in these cells to prevent the metastasis of cancer cells around the neighboring tissues. Because glucose is an integral component for cell proliferation, cancer cells cannot proliferate and hence […]<\/p>\n","protected":false},"author":1,"featured_media":7855,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"right-sidebar","site-content-layout":"plain-container","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"disabled","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"default","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"footnotes":""},"categories":[110],"tags":[66,68,65,67,43,70,61,63,64,62,69],"acf":[],"_links":{"self":[{"href":"https:\/\/artofhealingcancer.com\/wp-json\/wp\/v2\/posts\/7626"}],"collection":[{"href":"https:\/\/artofhealingcancer.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/artofhealingcancer.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/artofhealingcancer.com\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/artofhealingcancer.com\/wp-json\/wp\/v2\/comments?post=7626"}],"version-history":[{"count":2,"href":"https:\/\/artofhealingcancer.com\/wp-json\/wp\/v2\/posts\/7626\/revisions"}],"predecessor-version":[{"id":11438,"href":"https:\/\/artofhealingcancer.com\/wp-json\/wp\/v2\/posts\/7626\/revisions\/11438"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/artofhealingcancer.com\/wp-json\/wp\/v2\/media\/7855"}],"wp:attachment":[{"href":"https:\/\/artofhealingcancer.com\/wp-json\/wp\/v2\/media?parent=7626"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/artofhealingcancer.com\/wp-json\/wp\/v2\/categories?post=7626"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/artofhealingcancer.com\/wp-json\/wp\/v2\/tags?post=7626"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}