Chronic Dietary Administration of the Glycolytic Inhibitor 2-Deoxy-D-Glucose (2-DG) Inhibits the Growth of Implanted Ehrlich's Ascites Tumor in Mice
Dietary energy restriction (DER) has been well established as a potent anticancer strategy. Non-adoption of restricted diet for an extended period has limited its practical implementation in humans with a compelling need to develop agents that mimic effects similar to DER, without reduction in actua...
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creator | Singh, Saurabh Pandey, Sanjay Bhatt, Anant Narayan Chaudhary, Richa Bhuria, Vikas Kalra, Namita Soni, Ravi Roy, Bal Gangadhar Saluja, Daman Dwarakanath, Bilikere S |
description | Dietary energy restriction (DER) has been well established as a potent anticancer strategy. Non-adoption of restricted diet for an extended period has limited its practical implementation in humans with a compelling need to develop agents that mimic effects similar to DER, without reduction in actual dietary intake. Glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), has recently been shown to possess potential as an energy restriction mimetic agent (ERMA). In the present study we evaluated the effect of dietary 2-DG administration on a mouse tumor model, with a focus on several potential mechanisms that may account for the inhibition of tumorigenesis.
Swiss albino strain 'A' mice were administered with 0.2% and 0.4% w/v 2-DG in drinking water for 3 months prior to tumor implantation (Ehrlich's ascites carcinoma; EAC) and continued till the termination of the study with no adverse effects on general physiology and animal growth. Dietary 2-DG significantly reduced the tumor incidence, delayed the onset, and compromised the tumor growth along with enhanced survival. We observed reduced blood glucose and serum insulin levels along with decreased proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine positive (BrdU+) tumor cells in 2-DG fed mice. Also, reduced levels of certain key players of metabolic pathways such as phosphatidylinositol 3-kinase (PI3K), phosphorylated-Akt and hypoxia inducible factor-1 alpha (HIF-1α) were also noted in tumors of 2-DG fed mice. Further, decrease in CD4+/CD8+ ratio and T-regulatory cells observed in 2-DG fed mice suggested enhanced antitumor immunity and T cell effector function.
These results strongly suggest that dietary 2-DG administration in mice, at doses easily achievable in humans, suitably modulates several pleotrophic factors mimicking DER and inhibits tumorigenesis, emphasizing the use of ERMAs as a promising cancer preventive strategy. |
doi_str_mv | 10.1371/journal.pone.0132089 |
format | Article |
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Swiss albino strain 'A' mice were administered with 0.2% and 0.4% w/v 2-DG in drinking water for 3 months prior to tumor implantation (Ehrlich's ascites carcinoma; EAC) and continued till the termination of the study with no adverse effects on general physiology and animal growth. Dietary 2-DG significantly reduced the tumor incidence, delayed the onset, and compromised the tumor growth along with enhanced survival. We observed reduced blood glucose and serum insulin levels along with decreased proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine positive (BrdU+) tumor cells in 2-DG fed mice. Also, reduced levels of certain key players of metabolic pathways such as phosphatidylinositol 3-kinase (PI3K), phosphorylated-Akt and hypoxia inducible factor-1 alpha (HIF-1α) were also noted in tumors of 2-DG fed mice. Further, decrease in CD4+/CD8+ ratio and T-regulatory cells observed in 2-DG fed mice suggested enhanced antitumor immunity and T cell effector function.
These results strongly suggest that dietary 2-DG administration in mice, at doses easily achievable in humans, suitably modulates several pleotrophic factors mimicking DER and inhibits tumorigenesis, emphasizing the use of ERMAs as a promising cancer preventive strategy.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0132089</identifier><identifier>PMID: 26135741</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>1-Phosphatidylinositol 3-kinase ; Aging ; AKT protein ; Analysis ; Angiogenesis ; Animal growth ; Animals ; Antimetabolites, Antineoplastic - administration & dosage ; Antimetabolites, Antineoplastic - blood ; Antimetabolites, Antineoplastic - pharmacology ; Antimetabolites, Antineoplastic - therapeutic use ; Antineoplastic agents ; Ascites ; Biomedical research ; Biotechnology ; Blood glucose ; Blood Glucose - analysis ; Brain cancer ; Bromodeoxyuridine ; Caloric Restriction ; Cancer therapies ; Carcinoma, Ehrlich Tumor - blood supply ; Carcinoma, Ehrlich Tumor - drug therapy ; Carcinoma, Ehrlich Tumor - immunology ; CD4 antigen ; CD4-CD8 Ratio ; CD8 antigen ; Cell cycle ; Cell Division - drug effects ; Cytotoxicity ; Deoxyglucose - administration & dosage ; Deoxyglucose - blood ; Deoxyglucose - pharmacology ; Deoxyglucose - therapeutic use ; Diet ; Dietary intake ; Dietary restrictions ; Drinking water ; Drug Screening Assays, Antitumor ; Energy ; Female ; Glucose ; Glycolysis ; Glycolysis - drug effects ; Growth ; Hypoxia ; Immunity ; Immunoregulation ; Implantation ; Inhibitors ; Insulin ; Insulin - blood ; Insulin-like growth factors ; Ionizing radiation ; Kinases ; Laboratories ; Lymphocytes ; Lymphocytes T ; Matrix Metalloproteinase 9 - analysis ; Metabolic pathways ; Metabolism ; Mice ; Mimicry ; Neoplasm Proteins - physiology ; Neovascularization, Pathologic - drug therapy ; Nuclear medicine ; Physiological aspects ; Premedication ; Proliferating cell nuclear antigen ; Prostate ; Random Allocation ; Rodents ; Signal transduction ; Signal Transduction - drug effects ; T cells ; T-Lymphocytes, Regulatory - drug effects ; T-Lymphocytes, Regulatory - immunology ; Tumor Burden - drug effects ; Tumor cells ; Tumorigenesis ; Tumors</subject><ispartof>PloS one, 2015-07, Vol.10 (7), p.e0132089-e0132089</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Singh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Singh et al 2015 Singh et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-d47c56346ec7cd5e6d11dfa0ecfbb855b40fd32a1f9f2d4867830dbd70f95cfc3</citedby><cites>FETCH-LOGICAL-c758t-d47c56346ec7cd5e6d11dfa0ecfbb855b40fd32a1f9f2d4867830dbd70f95cfc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4489743/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4489743/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2926,23864,27922,27923,53789,53791,79370,79371</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26135741$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Huang, Cheng</contributor><creatorcontrib>Singh, Saurabh</creatorcontrib><creatorcontrib>Pandey, Sanjay</creatorcontrib><creatorcontrib>Bhatt, Anant Narayan</creatorcontrib><creatorcontrib>Chaudhary, Richa</creatorcontrib><creatorcontrib>Bhuria, Vikas</creatorcontrib><creatorcontrib>Kalra, Namita</creatorcontrib><creatorcontrib>Soni, Ravi</creatorcontrib><creatorcontrib>Roy, Bal Gangadhar</creatorcontrib><creatorcontrib>Saluja, Daman</creatorcontrib><creatorcontrib>Dwarakanath, Bilikere S</creatorcontrib><title>Chronic Dietary Administration of the Glycolytic Inhibitor 2-Deoxy-D-Glucose (2-DG) Inhibits the Growth of Implanted Ehrlich's Ascites Tumor in Mice</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Dietary energy restriction (DER) has been well established as a potent anticancer strategy. Non-adoption of restricted diet for an extended period has limited its practical implementation in humans with a compelling need to develop agents that mimic effects similar to DER, without reduction in actual dietary intake. Glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), has recently been shown to possess potential as an energy restriction mimetic agent (ERMA). In the present study we evaluated the effect of dietary 2-DG administration on a mouse tumor model, with a focus on several potential mechanisms that may account for the inhibition of tumorigenesis.
Swiss albino strain 'A' mice were administered with 0.2% and 0.4% w/v 2-DG in drinking water for 3 months prior to tumor implantation (Ehrlich's ascites carcinoma; EAC) and continued till the termination of the study with no adverse effects on general physiology and animal growth. Dietary 2-DG significantly reduced the tumor incidence, delayed the onset, and compromised the tumor growth along with enhanced survival. We observed reduced blood glucose and serum insulin levels along with decreased proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine positive (BrdU+) tumor cells in 2-DG fed mice. Also, reduced levels of certain key players of metabolic pathways such as phosphatidylinositol 3-kinase (PI3K), phosphorylated-Akt and hypoxia inducible factor-1 alpha (HIF-1α) were also noted in tumors of 2-DG fed mice. Further, decrease in CD4+/CD8+ ratio and T-regulatory cells observed in 2-DG fed mice suggested enhanced antitumor immunity and T cell effector function.
These results strongly suggest that dietary 2-DG administration in mice, at doses easily achievable in humans, suitably modulates several pleotrophic factors mimicking DER and inhibits tumorigenesis, emphasizing the use of ERMAs as a promising cancer preventive strategy.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>Aging</subject><subject>AKT protein</subject><subject>Analysis</subject><subject>Angiogenesis</subject><subject>Animal growth</subject><subject>Animals</subject><subject>Antimetabolites, Antineoplastic - administration & dosage</subject><subject>Antimetabolites, Antineoplastic - blood</subject><subject>Antimetabolites, Antineoplastic - pharmacology</subject><subject>Antimetabolites, Antineoplastic - therapeutic use</subject><subject>Antineoplastic agents</subject><subject>Ascites</subject><subject>Biomedical research</subject><subject>Biotechnology</subject><subject>Blood glucose</subject><subject>Blood Glucose - analysis</subject><subject>Brain cancer</subject><subject>Bromodeoxyuridine</subject><subject>Caloric Restriction</subject><subject>Cancer therapies</subject><subject>Carcinoma, Ehrlich Tumor - blood supply</subject><subject>Carcinoma, Ehrlich Tumor - drug therapy</subject><subject>Carcinoma, Ehrlich Tumor - immunology</subject><subject>CD4 antigen</subject><subject>CD4-CD8 Ratio</subject><subject>CD8 antigen</subject><subject>Cell cycle</subject><subject>Cell Division - drug effects</subject><subject>Cytotoxicity</subject><subject>Deoxyglucose - administration & dosage</subject><subject>Deoxyglucose - blood</subject><subject>Deoxyglucose - pharmacology</subject><subject>Deoxyglucose - therapeutic use</subject><subject>Diet</subject><subject>Dietary intake</subject><subject>Dietary restrictions</subject><subject>Drinking water</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Energy</subject><subject>Female</subject><subject>Glucose</subject><subject>Glycolysis</subject><subject>Glycolysis - drug effects</subject><subject>Growth</subject><subject>Hypoxia</subject><subject>Immunity</subject><subject>Immunoregulation</subject><subject>Implantation</subject><subject>Inhibitors</subject><subject>Insulin</subject><subject>Insulin - 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drug effects</subject><subject>Tumor cells</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk99u0zAYxSMEYmPwBggiIcF2kWLHjpPcIFXtKJWGJsHg1nL8p3HlxJ3twPoePDDu2k4t2gVKpFiff-c4PvaXJK8hGEFUwo9LO7iemdHK9nIEIMpBVT9JTmGN8ozkAD09GJ8kL7xfAlCgipDnyUlOICpKDE-TP5PW2V7zdKplYG6djkWne-2DY0HbPrUqDa1MZ2bNrVmHCM77Vjc6WJfm2VTau3U2zWZm4NbL9DyWZhd7xG-lzv4O7cZo3q0M64MU6WXrjObtB5-OPddB-vRm6KKj7tOvmsuXyTPFjJevdt-z5Mfny5vJl-zqejafjK8yXhZVyAQueUEQJpKXXBSSCAiFYkBy1TRVUTQYKIFyBlWtcoErUlYIiEaUQNUFVxydJW-3vitjPd0F6ikkNYJVDUkZifmWEJYt6crpLmZELdP0vmDdgjIXUzGSctIgWEZ_QCCu86ZuVNEowRhD8W1k9Pq0W21oOim47GPI5sj0eKbXLV3YXxTjqi4xigbnOwNnbwfpA-2059LEUKUd7v8b14SAHEf03T_o47vbUQsWN6B7ZeO6fGNKxzgHeVWiCkRq9AgVHyE7zePtUzrWjwQXR4LIBHkXFmzwns6_f_t_9vrnMfv-gG0lM6H11gybi-qPQbwFubPeO6keQoaAbppnnwbdNA_dNU-UvTk8oAfRvlvQXx-8Fcg</recordid><startdate>20150702</startdate><enddate>20150702</enddate><creator>Singh, Saurabh</creator><creator>Pandey, Sanjay</creator><creator>Bhatt, Anant Narayan</creator><creator>Chaudhary, Richa</creator><creator>Bhuria, Vikas</creator><creator>Kalra, Namita</creator><creator>Soni, Ravi</creator><creator>Roy, Bal Gangadhar</creator><creator>Saluja, Daman</creator><creator>Dwarakanath, Bilikere S</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150702</creationdate><title>Chronic Dietary Administration of the Glycolytic Inhibitor 2-Deoxy-D-Glucose (2-DG) Inhibits the Growth of Implanted Ehrlich's Ascites Tumor in Mice</title><author>Singh, Saurabh ; Pandey, Sanjay ; Bhatt, Anant Narayan ; Chaudhary, Richa ; Bhuria, Vikas ; Kalra, Namita ; Soni, Ravi ; Roy, Bal Gangadhar ; Saluja, Daman ; Dwarakanath, Bilikere S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-d47c56346ec7cd5e6d11dfa0ecfbb855b40fd32a1f9f2d4867830dbd70f95cfc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>Aging</topic><topic>AKT protein</topic><topic>Analysis</topic><topic>Angiogenesis</topic><topic>Animal growth</topic><topic>Animals</topic><topic>Antimetabolites, Antineoplastic - 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therapeutic use</topic><topic>Diet</topic><topic>Dietary intake</topic><topic>Dietary restrictions</topic><topic>Drinking water</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Energy</topic><topic>Female</topic><topic>Glucose</topic><topic>Glycolysis</topic><topic>Glycolysis - drug effects</topic><topic>Growth</topic><topic>Hypoxia</topic><topic>Immunity</topic><topic>Immunoregulation</topic><topic>Implantation</topic><topic>Inhibitors</topic><topic>Insulin</topic><topic>Insulin - blood</topic><topic>Insulin-like growth factors</topic><topic>Ionizing radiation</topic><topic>Kinases</topic><topic>Laboratories</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Matrix Metalloproteinase 9 - analysis</topic><topic>Metabolic pathways</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Mimicry</topic><topic>Neoplasm Proteins - physiology</topic><topic>Neovascularization, Pathologic - drug therapy</topic><topic>Nuclear medicine</topic><topic>Physiological aspects</topic><topic>Premedication</topic><topic>Proliferating cell nuclear antigen</topic><topic>Prostate</topic><topic>Random Allocation</topic><topic>Rodents</topic><topic>Signal transduction</topic><topic>Signal Transduction - drug effects</topic><topic>T cells</topic><topic>T-Lymphocytes, Regulatory - drug effects</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>Tumor Burden - drug effects</topic><topic>Tumor cells</topic><topic>Tumorigenesis</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Singh, Saurabh</creatorcontrib><creatorcontrib>Pandey, Sanjay</creatorcontrib><creatorcontrib>Bhatt, Anant Narayan</creatorcontrib><creatorcontrib>Chaudhary, Richa</creatorcontrib><creatorcontrib>Bhuria, Vikas</creatorcontrib><creatorcontrib>Kalra, Namita</creatorcontrib><creatorcontrib>Soni, Ravi</creatorcontrib><creatorcontrib>Roy, Bal Gangadhar</creatorcontrib><creatorcontrib>Saluja, Daman</creatorcontrib><creatorcontrib>Dwarakanath, Bilikere S</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>ProQuest_Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>https://resources.nclive.org/materials</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agriculture Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Singh, Saurabh</au><au>Pandey, Sanjay</au><au>Bhatt, Anant Narayan</au><au>Chaudhary, Richa</au><au>Bhuria, Vikas</au><au>Kalra, Namita</au><au>Soni, Ravi</au><au>Roy, Bal Gangadhar</au><au>Saluja, Daman</au><au>Dwarakanath, Bilikere S</au><au>Huang, Cheng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chronic Dietary Administration of the Glycolytic Inhibitor 2-Deoxy-D-Glucose (2-DG) Inhibits the Growth of Implanted Ehrlich's Ascites Tumor in Mice</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-07-02</date><risdate>2015</risdate><volume>10</volume><issue>7</issue><spage>e0132089</spage><epage>e0132089</epage><pages>e0132089-e0132089</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Dietary energy restriction (DER) has been well established as a potent anticancer strategy. Non-adoption of restricted diet for an extended period has limited its practical implementation in humans with a compelling need to develop agents that mimic effects similar to DER, without reduction in actual dietary intake. Glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), has recently been shown to possess potential as an energy restriction mimetic agent (ERMA). In the present study we evaluated the effect of dietary 2-DG administration on a mouse tumor model, with a focus on several potential mechanisms that may account for the inhibition of tumorigenesis.
Swiss albino strain 'A' mice were administered with 0.2% and 0.4% w/v 2-DG in drinking water for 3 months prior to tumor implantation (Ehrlich's ascites carcinoma; EAC) and continued till the termination of the study with no adverse effects on general physiology and animal growth. Dietary 2-DG significantly reduced the tumor incidence, delayed the onset, and compromised the tumor growth along with enhanced survival. We observed reduced blood glucose and serum insulin levels along with decreased proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine positive (BrdU+) tumor cells in 2-DG fed mice. Also, reduced levels of certain key players of metabolic pathways such as phosphatidylinositol 3-kinase (PI3K), phosphorylated-Akt and hypoxia inducible factor-1 alpha (HIF-1α) were also noted in tumors of 2-DG fed mice. Further, decrease in CD4+/CD8+ ratio and T-regulatory cells observed in 2-DG fed mice suggested enhanced antitumor immunity and T cell effector function.
These results strongly suggest that dietary 2-DG administration in mice, at doses easily achievable in humans, suitably modulates several pleotrophic factors mimicking DER and inhibits tumorigenesis, emphasizing the use of ERMAs as a promising cancer preventive strategy.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26135741</pmid><doi>10.1371/journal.pone.0132089</doi><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2015-07, Vol.10 (7), p.e0132089-e0132089 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_1693189167 |
source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; NCBI_PubMed Central(免费); Free E-Journal (出版社公開部分のみ); DOAJ Directory of Open Access Journals; Free Full-Text Journals in Chemistry |
subjects | 1-Phosphatidylinositol 3-kinase Aging AKT protein Analysis Angiogenesis Animal growth Animals Antimetabolites, Antineoplastic - administration & dosage Antimetabolites, Antineoplastic - blood Antimetabolites, Antineoplastic - pharmacology Antimetabolites, Antineoplastic - therapeutic use Antineoplastic agents Ascites Biomedical research Biotechnology Blood glucose Blood Glucose - analysis Brain cancer Bromodeoxyuridine Caloric Restriction Cancer therapies Carcinoma, Ehrlich Tumor - blood supply Carcinoma, Ehrlich Tumor - drug therapy Carcinoma, Ehrlich Tumor - immunology CD4 antigen CD4-CD8 Ratio CD8 antigen Cell cycle Cell Division - drug effects Cytotoxicity Deoxyglucose - administration & dosage Deoxyglucose - blood Deoxyglucose - pharmacology Deoxyglucose - therapeutic use Diet Dietary intake Dietary restrictions Drinking water Drug Screening Assays, Antitumor Energy Female Glucose Glycolysis Glycolysis - drug effects Growth Hypoxia Immunity Immunoregulation Implantation Inhibitors Insulin Insulin - blood Insulin-like growth factors Ionizing radiation Kinases Laboratories Lymphocytes Lymphocytes T Matrix Metalloproteinase 9 - analysis Metabolic pathways Metabolism Mice Mimicry Neoplasm Proteins - physiology Neovascularization, Pathologic - drug therapy Nuclear medicine Physiological aspects Premedication Proliferating cell nuclear antigen Prostate Random Allocation Rodents Signal transduction Signal Transduction - drug effects T cells T-Lymphocytes, Regulatory - drug effects T-Lymphocytes, Regulatory - immunology Tumor Burden - drug effects Tumor cells Tumorigenesis Tumors |
title | Chronic Dietary Administration of the Glycolytic Inhibitor 2-Deoxy-D-Glucose (2-DG) Inhibits the Growth of Implanted Ehrlich's Ascites Tumor in Mice |
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