Oroxylin A induces dissociation of hexokinase II from the mitochondria and inhibits glycolysis by SIRT3-mediated deacetylation of cyclophilin D in breast carcinoma
Oroxylin A is a major active component of the Chinese traditional medicinal plant Scutellaria baicalensis Georgi , which has been reported as a potential anticancer drug. We demonstrated that, Oroxylin A inhibited the glycolysis and the binding of hexokinase II (HK II) with mitochondria in human bre...
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description | Oroxylin A is a major active component of the Chinese traditional medicinal plant
Scutellaria baicalensis Georgi
, which has been reported as a potential anticancer drug. We demonstrated that, Oroxylin A inhibited the glycolysis and the binding of hexokinase II (HK II) with mitochondria in human breast carcinoma cell lines, which was dependent on sirtuin-3 (SIRT3). The level of SIRT3 in mitochondria was increased by Oroxylin A. Then SIRT3 deacetylated cyclophilin D, diminished its peptidyl-prolyl
cis
-
trans
isomerase activity and induced its dissociation from the adenine nucleotide translocator. Finally, SIRT3-induced inactivation of cyclophilin D resulted in the detachment of mitochondrial HK II and the inhibition of glycolysis. These results have important implications for the metabolism reprogramming effect and the susceptibility to Oroxylin A-induced mitochondrial cytotoxicity through the regulation of SIRT3 in breast carcinoma. |
doi_str_mv | 10.1038/cddis.2013.131 |
format | Article |
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Scutellaria baicalensis Georgi
, which has been reported as a potential anticancer drug. We demonstrated that, Oroxylin A inhibited the glycolysis and the binding of hexokinase II (HK II) with mitochondria in human breast carcinoma cell lines, which was dependent on sirtuin-3 (SIRT3). The level of SIRT3 in mitochondria was increased by Oroxylin A. Then SIRT3 deacetylated cyclophilin D, diminished its peptidyl-prolyl
cis
-
trans
isomerase activity and induced its dissociation from the adenine nucleotide translocator. Finally, SIRT3-induced inactivation of cyclophilin D resulted in the detachment of mitochondrial HK II and the inhibition of glycolysis. These results have important implications for the metabolism reprogramming effect and the susceptibility to Oroxylin A-induced mitochondrial cytotoxicity through the regulation of SIRT3 in breast carcinoma.</description><identifier>ISSN: 2041-4889</identifier><identifier>EISSN: 2041-4889</identifier><identifier>DOI: 10.1038/cddis.2013.131</identifier><identifier>PMID: 23598413</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/67/1347 ; 631/67/2327 ; 631/80/82/23 ; 631/92/349 ; Antibodies ; Biochemistry ; Biomedical and Life Sciences ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Cell Biology ; Cell Culture ; Cell Line, Tumor ; Cell Nucleus - metabolism ; Cyclophilins - genetics ; Cyclophilins - metabolism ; Female ; Flavonoids - chemistry ; Flavonoids - pharmacology ; Glycolysis - drug effects ; Hexokinase - metabolism ; Humans ; Immunology ; Life Sciences ; MCF-7 Cells ; Mitochondria - drug effects ; Mitochondria - metabolism ; Original ; original-article ; Oxidative Stress ; Peptidyl-Prolyl Isomerase F ; Plant Roots - chemistry ; RNA Interference ; RNA, Small Interfering - metabolism ; Scutellaria - chemistry ; Sirtuin 3 - antagonists & inhibitors ; Sirtuin 3 - genetics ; Sirtuin 3 - metabolism</subject><ispartof>Cell death & disease, 2013-04, Vol.4 (4), p.e601-e601</ispartof><rights>The Author(s) 2013</rights><rights>Copyright Nature Publishing Group Apr 2013</rights><rights>Copyright © 2013 Macmillan Publishers Limited 2013 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c557t-941843455588a1ec2541d94a335ae0985364797e9c15789c68009f2a26f8dab13</citedby><cites>FETCH-LOGICAL-c557t-941843455588a1ec2541d94a335ae0985364797e9c15789c68009f2a26f8dab13</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/PMC3641353/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641353/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27922,27923,41118,42187,51574,53789,53791</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23598413$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wei, L</creatorcontrib><creatorcontrib>Zhou, Y</creatorcontrib><creatorcontrib>Dai, Q</creatorcontrib><creatorcontrib>Qiao, C</creatorcontrib><creatorcontrib>Zhao, L</creatorcontrib><creatorcontrib>Hui, H</creatorcontrib><creatorcontrib>Lu, N</creatorcontrib><creatorcontrib>Guo, Q-L</creatorcontrib><title>Oroxylin A induces dissociation of hexokinase II from the mitochondria and inhibits glycolysis by SIRT3-mediated deacetylation of cyclophilin D in breast carcinoma</title><title>Cell death & disease</title><addtitle>Cell Death Dis</addtitle><addtitle>Cell Death Dis</addtitle><description>Oroxylin A is a major active component of the Chinese traditional medicinal plant
Scutellaria baicalensis Georgi
, which has been reported as a potential anticancer drug. We demonstrated that, Oroxylin A inhibited the glycolysis and the binding of hexokinase II (HK II) with mitochondria in human breast carcinoma cell lines, which was dependent on sirtuin-3 (SIRT3). The level of SIRT3 in mitochondria was increased by Oroxylin A. Then SIRT3 deacetylated cyclophilin D, diminished its peptidyl-prolyl
cis
-
trans
isomerase activity and induced its dissociation from the adenine nucleotide translocator. Finally, SIRT3-induced inactivation of cyclophilin D resulted in the detachment of mitochondrial HK II and the inhibition of glycolysis. These results have important implications for the metabolism reprogramming effect and the susceptibility to Oroxylin A-induced mitochondrial cytotoxicity through the regulation of SIRT3 in breast carcinoma.</description><subject>631/67/1347</subject><subject>631/67/2327</subject><subject>631/80/82/23</subject><subject>631/92/349</subject><subject>Antibodies</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Cell Biology</subject><subject>Cell Culture</subject><subject>Cell Line, Tumor</subject><subject>Cell Nucleus - metabolism</subject><subject>Cyclophilins - genetics</subject><subject>Cyclophilins - metabolism</subject><subject>Female</subject><subject>Flavonoids - chemistry</subject><subject>Flavonoids - pharmacology</subject><subject>Glycolysis - drug effects</subject><subject>Hexokinase - metabolism</subject><subject>Humans</subject><subject>Immunology</subject><subject>Life Sciences</subject><subject>MCF-7 Cells</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - metabolism</subject><subject>Original</subject><subject>original-article</subject><subject>Oxidative Stress</subject><subject>Peptidyl-Prolyl Isomerase F</subject><subject>Plant Roots - chemistry</subject><subject>RNA Interference</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Scutellaria - chemistry</subject><subject>Sirtuin 3 - antagonists & inhibitors</subject><subject>Sirtuin 3 - genetics</subject><subject>Sirtuin 3 - metabolism</subject><issn>2041-4889</issn><issn>2041-4889</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNptkkFvFCEUxydGY5vaq0dD4sXLbGGAGbiYNNXqJk2aaD0TBt7sUGdghRnT-Tx-0bJu3axGLpC8Hz_-L7yieE3wimAqLoy1Lq0qTOiKUPKsOK0wIyUTQj4_Op8U5ynd47woxRWvXxYnFeVSMEJPi1-3MTwsg_PoEjlvZwMJZWkKxunJBY9Ch3p4CN-d1wnQeo26GEY09YBGNwXTB2-j00h7m-_3rnVTQpthMWFYkkuoXdDX9Zc7Wo5gsxEssqANTMtw0JvFDGHbu12ID1mC2gg6TcjoaJwPo35VvOj0kOD8aT8rvl1_vLv6XN7cflpfXd6UhvNmKiUjglHGORdCEzAVZ8RKpinlGrAUnNaskQ1IQ3gjpKkFxrKrdFV3wuqW0LPi_d67ndsc14Cfoh7UNrpRx0UF7dTfFe96tQk_VRYTymkWvHsSxPBjhjSp0SUDw6A9hDkp0kgsaQ5bZ_TtP-h9mKPP7WVK1BVhpG4ytdpTJoaUInSHMASr3Qio3yOgdiOg8gjkC2-OWzjgfz48Axd7IOWS30A8evf_yke5QL8V</recordid><startdate>20130401</startdate><enddate>20130401</enddate><creator>Wei, L</creator><creator>Zhou, Y</creator><creator>Dai, Q</creator><creator>Qiao, C</creator><creator>Zhao, L</creator><creator>Hui, H</creator><creator>Lu, N</creator><creator>Guo, Q-L</creator><general>Nature Publishing Group UK</general><general>Springer Nature B.V</general><general>Nature Publishing Group</general><scope>C6C</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7TO</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20130401</creationdate><title>Oroxylin A induces dissociation of hexokinase II from the mitochondria and inhibits glycolysis by SIRT3-mediated deacetylation of cyclophilin D in breast carcinoma</title><author>Wei, L ; Zhou, Y ; Dai, Q ; Qiao, C ; Zhao, L ; Hui, H ; Lu, N ; Guo, Q-L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c557t-941843455588a1ec2541d94a335ae0985364797e9c15789c68009f2a26f8dab13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>631/67/1347</topic><topic>631/67/2327</topic><topic>631/80/82/23</topic><topic>631/92/349</topic><topic>Antibodies</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - pathology</topic><topic>Cell Biology</topic><topic>Cell Culture</topic><topic>Cell Line, Tumor</topic><topic>Cell Nucleus - metabolism</topic><topic>Cyclophilins - genetics</topic><topic>Cyclophilins - metabolism</topic><topic>Female</topic><topic>Flavonoids - chemistry</topic><topic>Flavonoids - pharmacology</topic><topic>Glycolysis - drug effects</topic><topic>Hexokinase - metabolism</topic><topic>Humans</topic><topic>Immunology</topic><topic>Life Sciences</topic><topic>MCF-7 Cells</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - metabolism</topic><topic>Original</topic><topic>original-article</topic><topic>Oxidative Stress</topic><topic>Peptidyl-Prolyl Isomerase F</topic><topic>Plant Roots - chemistry</topic><topic>RNA Interference</topic><topic>RNA, Small Interfering - metabolism</topic><topic>Scutellaria - chemistry</topic><topic>Sirtuin 3 - antagonists & inhibitors</topic><topic>Sirtuin 3 - genetics</topic><topic>Sirtuin 3 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wei, L</creatorcontrib><creatorcontrib>Zhou, Y</creatorcontrib><creatorcontrib>Dai, Q</creatorcontrib><creatorcontrib>Qiao, C</creatorcontrib><creatorcontrib>Zhao, L</creatorcontrib><creatorcontrib>Hui, H</creatorcontrib><creatorcontrib>Lu, N</creatorcontrib><creatorcontrib>Guo, Q-L</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech 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>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell death & disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wei, L</au><au>Zhou, Y</au><au>Dai, Q</au><au>Qiao, C</au><au>Zhao, L</au><au>Hui, H</au><au>Lu, N</au><au>Guo, Q-L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Oroxylin A induces dissociation of hexokinase II from the mitochondria and inhibits glycolysis by SIRT3-mediated deacetylation of cyclophilin D in breast carcinoma</atitle><jtitle>Cell death & disease</jtitle><stitle>Cell Death Dis</stitle><addtitle>Cell Death Dis</addtitle><date>2013-04-01</date><risdate>2013</risdate><volume>4</volume><issue>4</issue><spage>e601</spage><epage>e601</epage><pages>e601-e601</pages><issn>2041-4889</issn><eissn>2041-4889</eissn><abstract>Oroxylin A is a major active component of the Chinese traditional medicinal plant
Scutellaria baicalensis Georgi
, which has been reported as a potential anticancer drug. We demonstrated that, Oroxylin A inhibited the glycolysis and the binding of hexokinase II (HK II) with mitochondria in human breast carcinoma cell lines, which was dependent on sirtuin-3 (SIRT3). The level of SIRT3 in mitochondria was increased by Oroxylin A. Then SIRT3 deacetylated cyclophilin D, diminished its peptidyl-prolyl
cis
-
trans
isomerase activity and induced its dissociation from the adenine nucleotide translocator. Finally, SIRT3-induced inactivation of cyclophilin D resulted in the detachment of mitochondrial HK II and the inhibition of glycolysis. These results have important implications for the metabolism reprogramming effect and the susceptibility to Oroxylin A-induced mitochondrial cytotoxicity through the regulation of SIRT3 in breast carcinoma.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>23598413</pmid><doi>10.1038/cddis.2013.131</doi><oa>free_for_read</oa></addata></record> |
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subjects | 631/67/1347 631/67/2327 631/80/82/23 631/92/349 Antibodies Biochemistry Biomedical and Life Sciences Breast Neoplasms - metabolism Breast Neoplasms - pathology Cell Biology Cell Culture Cell Line, Tumor Cell Nucleus - metabolism Cyclophilins - genetics Cyclophilins - metabolism Female Flavonoids - chemistry Flavonoids - pharmacology Glycolysis - drug effects Hexokinase - metabolism Humans Immunology Life Sciences MCF-7 Cells Mitochondria - drug effects Mitochondria - metabolism Original original-article Oxidative Stress Peptidyl-Prolyl Isomerase F Plant Roots - chemistry RNA Interference RNA, Small Interfering - metabolism Scutellaria - chemistry Sirtuin 3 - antagonists & inhibitors Sirtuin 3 - genetics Sirtuin 3 - metabolism |
title | Oroxylin A induces dissociation of hexokinase II from the mitochondria and inhibits glycolysis by SIRT3-mediated deacetylation of cyclophilin D in breast carcinoma |
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