Upregulation of energy metabolism-related, p53-target TIGAR and SCO2 in HuH-7 cells with p53 mutation by geranylgeranoic acid treatment
Metabolic alternation in cancer cells is one of the most common characteristics that distinguish malignant cells from normal cells. Many studies have explained the Warburg hypothesis that cancer cells obtain more energy from aerobic glycolysis than mitochondrial respiration. Here, we show that a bra...
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| Veröffentlicht in: | Biomedical Research 2015/12/01, Vol.36(6), pp.371-381 |
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| description | Metabolic alternation in cancer cells is one of the most common characteristics that distinguish malignant cells from normal cells. Many studies have explained the Warburg hypothesis that cancer cells obtain more energy from aerobic glycolysis than mitochondrial respiration. Here, we show that a branched-chain C-20 polyunsaturated fatty acid, geranylgeranoic acid (GGA), induces upregulation of the cellular protein levels of TP53-induced glycolysis and apoptosis regulator (TIGAR) and synthesis of cytochrome c oxidase 2 (SCO2) in human hepatoma-derived HuH-7cells harboring the mutant TP53 gene, suggesting that GGA may shift an energetic state of the tumor cells from aerobic glycolysis to mitochondrial respiration. In addition, UPLC/TOF/MS-based metabolomics analysis supported the GGA-induced energetic shift, as it revealed that GGA induced a time-dependent increase in the cellular contents of fructose 6-phosphate and decrease of fructose 1,6-diphosphate. Furthermore, metabolomics analysis revealed that GGA rapidly induced spermine accumulation with slight decrease of spermidine. Taken together, the present study strongly suggests that GGA may shift HuH-7 cells from aerobic glycolysis to mitochondrial respiration through the immediate upregulation of TIGAR and SCO2 protein levels. |
| doi_str_mv | 10.2220/biomedres.36.371 |
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Many studies have explained the Warburg hypothesis that cancer cells obtain more energy from aerobic glycolysis than mitochondrial respiration. Here, we show that a branched-chain C-20 polyunsaturated fatty acid, geranylgeranoic acid (GGA), induces upregulation of the cellular protein levels of TP53-induced glycolysis and apoptosis regulator (TIGAR) and synthesis of cytochrome c oxidase 2 (SCO2) in human hepatoma-derived HuH-7cells harboring the mutant TP53 gene, suggesting that GGA may shift an energetic state of the tumor cells from aerobic glycolysis to mitochondrial respiration. In addition, UPLC/TOF/MS-based metabolomics analysis supported the GGA-induced energetic shift, as it revealed that GGA induced a time-dependent increase in the cellular contents of fructose 6-phosphate and decrease of fructose 1,6-diphosphate. Furthermore, metabolomics analysis revealed that GGA rapidly induced spermine accumulation with slight decrease of spermidine. Taken together, the present study strongly suggests that GGA may shift HuH-7 cells from aerobic glycolysis to mitochondrial respiration through the immediate upregulation of TIGAR and SCO2 protein levels.</description><identifier>ISSN: 0388-6107</identifier><identifier>EISSN: 1880-313X</identifier><identifier>DOI: 10.2220/biomedres.36.371</identifier><identifier>PMID: 26700591</identifier><language>eng</language><publisher>Japan: Biomedical Research Press</publisher><subject>Apoptosis - drug effects ; Apoptosis Regulatory Proteins ; Carcinoma, Hepatocellular - metabolism ; Carrier Proteins - genetics ; Carrier Proteins - metabolism ; Cell Line, Tumor ; Diterpenes - pharmacology ; Fatty Acids, Unsaturated - pharmacology ; Fructosediphosphates - metabolism ; Fructosephosphates - metabolism ; Glycolysis ; Humans ; Intracellular Signaling Peptides and Proteins - genetics ; Intracellular Signaling Peptides and Proteins - metabolism ; Liver Neoplasms - metabolism ; Metabolomics ; Mitochondrial Proteins - genetics ; Mitochondrial Proteins - metabolism ; Multivariate Analysis ; Mutation ; Tumor Suppressor Protein p53 - genetics ; Tumor Suppressor Protein p53 - metabolism ; Up-Regulation</subject><ispartof>Biomedical Research, 2015/12/01, Vol.36(6), pp.371-381</ispartof><rights>2015 Biomedical Research Press</rights><rights>Copyright Japan Science and Technology Agency 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c510t-5ae885281aac80e0e552bf215023983c0519882a03c1481091bca7cf7c07fa2f3</citedby><cites>FETCH-LOGICAL-c510t-5ae885281aac80e0e552bf215023983c0519882a03c1481091bca7cf7c07fa2f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,1885,27931,27932</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26700591$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>IWAO, Chieko</creatorcontrib><creatorcontrib>SHIDOJI, Yoshihiro</creatorcontrib><title>Upregulation of energy metabolism-related, p53-target TIGAR and SCO2 in HuH-7 cells with p53 mutation by geranylgeranoic acid treatment</title><title>Biomedical Research</title><addtitle>Biomed. Res.</addtitle><description>Metabolic alternation in cancer cells is one of the most common characteristics that distinguish malignant cells from normal cells. Many studies have explained the Warburg hypothesis that cancer cells obtain more energy from aerobic glycolysis than mitochondrial respiration. Here, we show that a branched-chain C-20 polyunsaturated fatty acid, geranylgeranoic acid (GGA), induces upregulation of the cellular protein levels of TP53-induced glycolysis and apoptosis regulator (TIGAR) and synthesis of cytochrome c oxidase 2 (SCO2) in human hepatoma-derived HuH-7cells harboring the mutant TP53 gene, suggesting that GGA may shift an energetic state of the tumor cells from aerobic glycolysis to mitochondrial respiration. In addition, UPLC/TOF/MS-based metabolomics analysis supported the GGA-induced energetic shift, as it revealed that GGA induced a time-dependent increase in the cellular contents of fructose 6-phosphate and decrease of fructose 1,6-diphosphate. Furthermore, metabolomics analysis revealed that GGA rapidly induced spermine accumulation with slight decrease of spermidine. Taken together, the present study strongly suggests that GGA may shift HuH-7 cells from aerobic glycolysis to mitochondrial respiration through the immediate upregulation of TIGAR and SCO2 protein levels.</description><subject>Apoptosis - drug effects</subject><subject>Apoptosis Regulatory Proteins</subject><subject>Carcinoma, Hepatocellular - metabolism</subject><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Diterpenes - pharmacology</subject><subject>Fatty Acids, Unsaturated - pharmacology</subject><subject>Fructosediphosphates - metabolism</subject><subject>Fructosephosphates - metabolism</subject><subject>Glycolysis</subject><subject>Humans</subject><subject>Intracellular Signaling Peptides and Proteins - genetics</subject><subject>Intracellular Signaling Peptides and Proteins - metabolism</subject><subject>Liver Neoplasms - metabolism</subject><subject>Metabolomics</subject><subject>Mitochondrial Proteins - genetics</subject><subject>Mitochondrial Proteins - metabolism</subject><subject>Multivariate Analysis</subject><subject>Mutation</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><subject>Up-Regulation</subject><issn>0388-6107</issn><issn>1880-313X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1rGzEQhkVpaNy0956KoJceus5Isna1x2DaOBAI5AN6W2bl2Y3MfriSluBf0L9duXYN7amnQbzPPJJ4GfsgYC6lhMvajT2tPYW5yueqEK_YTBgDmRLq-2s2A2VMlgsoztnbEDaQzsKoN-xc5gWALsWM_XzaemqnDqMbBz42nAby7Y73FLEeOxf6zFNKaf2Fb7XKIvqWIn-8ub665zis-cPyTnI38NW0ygpuqesCf3HxeU_zfooHcb3jLXkcdt3vMTrL0bo1j54w9jTEd-yswS7Q--O8YE_fvj4uV9nt3fXN8uo2s1pAzDSSMVoagWgNEJDWsm6k0CBVaZQFLUpjJIKyYmEElKK2WNimsFA0KBt1wT4fvFs__pgoxKp3Yf9qHGicQiWKXCpthF78B5ouK3OlZUI__YNuxskP6SN7SsJClwtIFBwo68cQPDXV1rse_a4SUO37rE59ViqvUp9p5eNRPNUpOS38KTABywOwCRFbOgHoo7Md_W3Mj9pTap_RVzSoX2XhtQg</recordid><startdate>20150101</startdate><enddate>20150101</enddate><creator>IWAO, Chieko</creator><creator>SHIDOJI, Yoshihiro</creator><general>Biomedical Research Press</general><general>Japan Science and Technology Agency</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>7QO</scope><scope>7QP</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>7TO</scope><scope>H94</scope></search><sort><creationdate>20150101</creationdate><title>Upregulation of energy metabolism-related, p53-target TIGAR and SCO2 in HuH-7 cells with p53 mutation by geranylgeranoic acid treatment</title><author>IWAO, Chieko ; SHIDOJI, Yoshihiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c510t-5ae885281aac80e0e552bf215023983c0519882a03c1481091bca7cf7c07fa2f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Apoptosis - drug effects</topic><topic>Apoptosis Regulatory Proteins</topic><topic>Carcinoma, Hepatocellular - metabolism</topic><topic>Carrier Proteins - genetics</topic><topic>Carrier Proteins - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Diterpenes - pharmacology</topic><topic>Fatty Acids, Unsaturated - pharmacology</topic><topic>Fructosediphosphates - metabolism</topic><topic>Fructosephosphates - metabolism</topic><topic>Glycolysis</topic><topic>Humans</topic><topic>Intracellular Signaling Peptides and Proteins - genetics</topic><topic>Intracellular Signaling Peptides and Proteins - metabolism</topic><topic>Liver Neoplasms - metabolism</topic><topic>Metabolomics</topic><topic>Mitochondrial Proteins - genetics</topic><topic>Mitochondrial Proteins - metabolism</topic><topic>Multivariate Analysis</topic><topic>Mutation</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>IWAO, Chieko</creatorcontrib><creatorcontrib>SHIDOJI, Yoshihiro</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Biomedical Research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>IWAO, Chieko</au><au>SHIDOJI, Yoshihiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Upregulation of energy metabolism-related, p53-target TIGAR and SCO2 in HuH-7 cells with p53 mutation by geranylgeranoic acid treatment</atitle><jtitle>Biomedical Research</jtitle><addtitle>Biomed. Res.</addtitle><date>2015-01-01</date><risdate>2015</risdate><volume>36</volume><issue>6</issue><spage>371</spage><epage>381</epage><pages>371-381</pages><issn>0388-6107</issn><eissn>1880-313X</eissn><abstract>Metabolic alternation in cancer cells is one of the most common characteristics that distinguish malignant cells from normal cells. Many studies have explained the Warburg hypothesis that cancer cells obtain more energy from aerobic glycolysis than mitochondrial respiration. Here, we show that a branched-chain C-20 polyunsaturated fatty acid, geranylgeranoic acid (GGA), induces upregulation of the cellular protein levels of TP53-induced glycolysis and apoptosis regulator (TIGAR) and synthesis of cytochrome c oxidase 2 (SCO2) in human hepatoma-derived HuH-7cells harboring the mutant TP53 gene, suggesting that GGA may shift an energetic state of the tumor cells from aerobic glycolysis to mitochondrial respiration. In addition, UPLC/TOF/MS-based metabolomics analysis supported the GGA-induced energetic shift, as it revealed that GGA induced a time-dependent increase in the cellular contents of fructose 6-phosphate and decrease of fructose 1,6-diphosphate. Furthermore, metabolomics analysis revealed that GGA rapidly induced spermine accumulation with slight decrease of spermidine. Taken together, the present study strongly suggests that GGA may shift HuH-7 cells from aerobic glycolysis to mitochondrial respiration through the immediate upregulation of TIGAR and SCO2 protein levels.</abstract><cop>Japan</cop><pub>Biomedical Research Press</pub><pmid>26700591</pmid><doi>10.2220/biomedres.36.371</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Apoptosis - drug effects Apoptosis Regulatory Proteins Carcinoma, Hepatocellular - metabolism Carrier Proteins - genetics Carrier Proteins - metabolism Cell Line, Tumor Diterpenes - pharmacology Fatty Acids, Unsaturated - pharmacology Fructosediphosphates - metabolism Fructosephosphates - metabolism Glycolysis Humans Intracellular Signaling Peptides and Proteins - genetics Intracellular Signaling Peptides and Proteins - metabolism Liver Neoplasms - metabolism Metabolomics Mitochondrial Proteins - genetics Mitochondrial Proteins - metabolism Multivariate Analysis Mutation Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism Up-Regulation |
| title | Upregulation of energy metabolism-related, p53-target TIGAR and SCO2 in HuH-7 cells with p53 mutation by geranylgeranoic acid treatment |
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