5-demethyltangeretin inhibits human non-small cell lung cancer cell growth by inducing G2/M cell cycle arrest and apoptosis
Identifieur interne : 001384 ( Ncbi/Merge ); précédent : 001383; suivant : 0013855-demethyltangeretin inhibits human non-small cell lung cancer cell growth by inducing G2/M cell cycle arrest and apoptosis
Auteurs : Noppawat Charoensinphon [États-Unis] ; Peiju Qiu [États-Unis, République populaire de Chine] ; Ping Dong [États-Unis] ; Jinkai Zheng [États-Unis] ; Pearline Ngauv [États-Unis] ; Yong Cao [République populaire de Chine] ; Shiming Li [États-Unis] ; Chi-Tang Ho [États-Unis] ; Hang Xiao [États-Unis]Source :
- Molecular nutrition & food research [ 1613-4125 ] ; 2013.
Abstract
Tangeretin and 5-demethyltangeretin (5DT) are two closely related polymethoxyflavones found in citrus fruits. We investigated growth inhibitory effects on three human non-small cell lung cancer (NSCLC) cells.
Cell viability assay demonstrated that 5DT inhibited NSCLC cell growth in a time- and dose-dependent manner, and IC50s of 5DT were 79-fold, 57-fold and 56-fold lower than those of tangeretin in A549, H460, and H1299 cells, respectively. Flow cytometry analysis showed that 5DT induced extensive G2/M cell cycle arrest and apoptosis in NSCLC cells, while tangeretin at 10-fold higher concentrations did not. The apoptosis induced by 5DT was further confirmed by activation of caspase-3 and cleavage of PARP. Moreover, 5DT dose-dependently upregulated p53 and p21Cip1/Waf1, and downregulated Cdc-2 (Cdk-1) and cyclin B1. HPLC analysis revealed that the intracellular levels of 5DT in NSCLC cells were 2.7 - 4.9-fold higher than those of tangeretin after the cells were treated with 5DT or tangeretin at the same concentration.
our results demonstrated that 5DT inhibited NSCLC cell growth by inducing G2/M cell cycle arrest and apoptosis. These effects were much stronger than those produced by tangeretin, which is partially due to the higher intracellular uptake of 5DT than tangeretin.
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DOI: 10.1002/mnfr.201300136
PubMed: 23926120
PubMed Central: 4648632
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id="A1">Department of Food Science, University of Massachusetts, Amherst, MA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Food Science, University of Massachusetts, Amherst, MA</wicri:regionArea><orgName type="university">Université du Massachusetts</orgName><placeName><settlement type="city">Amherst (Massachusetts)</settlement><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Zheng, Jinkai" sort="Zheng, Jinkai" uniqKey="Zheng J" first="Jinkai" last="Zheng">Jinkai Zheng</name><affiliation wicri:level="4"><nlm:aff id="A1">Department of Food Science, University of Massachusetts, Amherst, MA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Food Science, University of Massachusetts, Amherst, MA</wicri:regionArea><orgName type="university">Université du Massachusetts</orgName><placeName><settlement type="city">Amherst (Massachusetts)</settlement><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Ngauv, Pearline" sort="Ngauv, Pearline" uniqKey="Ngauv P" first="Pearline" last="Ngauv">Pearline Ngauv</name><affiliation wicri:level="4"><nlm:aff id="A1">Department of Food Science, University of Massachusetts, Amherst, MA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Food Science, University of Massachusetts, Amherst, MA</wicri:regionArea><orgName type="university">Université du Massachusetts</orgName><placeName><settlement type="city">Amherst (Massachusetts)</settlement><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Cao, Yong" sort="Cao, Yong" uniqKey="Cao Y" first="Yong" last="Cao">Yong Cao</name><affiliation wicri:level="1"><nlm:aff id="A3">College of Food Science, South China Agricultural University, Guangzhou, Guangdong, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Food Science, South China Agricultural University, Guangzhou, Guangdong</wicri:regionArea><wicri:noRegion>Guangdong</wicri:noRegion></affiliation></author><author><name sortKey="Li, Shiming" sort="Li, Shiming" uniqKey="Li S" first="Shiming" last="Li">Shiming Li</name><affiliation wicri:level="1"><nlm:aff id="A4">Department of Food Science, Rutgers, the State University of New Jersey, New Brunswick, NJ, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Food Science, Rutgers, the State University of New Jersey, New Brunswick, NJ</wicri:regionArea><wicri:noRegion>NJ</wicri:noRegion></affiliation></author><author><name sortKey="Ho, Chi Tang" sort="Ho, Chi Tang" uniqKey="Ho C" first="Chi-Tang" last="Ho">Chi-Tang Ho</name><affiliation wicri:level="1"><nlm:aff id="A4">Department of Food Science, Rutgers, the State University of New Jersey, New Brunswick, NJ, USA</nlm:aff><country 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type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648632</idno><idno type="RBID">PMC:4648632</idno><idno type="doi">10.1002/mnfr.201300136</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000D66</idno><idno type="wicri:Area/Pmc/Curation">000D65</idno><idno type="wicri:Area/Pmc/Checkpoint">000B87</idno><idno type="wicri:Area/Ncbi/Merge">001384</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">5-demethyltangeretin inhibits human non-small cell lung cancer cell growth by inducing G2/M cell cycle arrest and apoptosis</title><author><name sortKey="Charoensinphon, Noppawat" sort="Charoensinphon, Noppawat" uniqKey="Charoensinphon N" first="Noppawat" last="Charoensinphon">Noppawat Charoensinphon</name><affiliation wicri:level="4"><nlm:aff id="A1">Department of Food Science, University of Massachusetts, Amherst, MA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Food Science, 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China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Marine Drug and Food Institute, Ocean University of China, Qingdao, Shandong</wicri:regionArea><wicri:noRegion>Shandong</wicri:noRegion></affiliation></author><author><name sortKey="Dong, Ping" sort="Dong, Ping" uniqKey="Dong P" first="Ping" last="Dong">Ping Dong</name><affiliation wicri:level="4"><nlm:aff id="A1">Department of Food Science, University of Massachusetts, Amherst, MA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Food Science, University of Massachusetts, Amherst, MA</wicri:regionArea><orgName type="university">Université du Massachusetts</orgName><placeName><settlement type="city">Amherst (Massachusetts)</settlement><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Zheng, Jinkai" sort="Zheng, Jinkai" uniqKey="Zheng J" first="Jinkai" last="Zheng">Jinkai Zheng</name><affiliation wicri:level="4"><nlm:aff id="A1">Department of Food Science, University of Massachusetts, Amherst, MA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Food Science, University of Massachusetts, Amherst, MA</wicri:regionArea><orgName type="university">Université du Massachusetts</orgName><placeName><settlement type="city">Amherst (Massachusetts)</settlement><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Ngauv, Pearline" sort="Ngauv, Pearline" uniqKey="Ngauv P" first="Pearline" last="Ngauv">Pearline Ngauv</name><affiliation wicri:level="4"><nlm:aff id="A1">Department of Food Science, University of Massachusetts, Amherst, MA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Food Science, University of Massachusetts, Amherst, MA</wicri:regionArea><orgName type="university">Université du Massachusetts</orgName><placeName><settlement type="city">Amherst (Massachusetts)</settlement><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Cao, Yong" sort="Cao, Yong" uniqKey="Cao Y" first="Yong" last="Cao">Yong Cao</name><affiliation wicri:level="1"><nlm:aff id="A3">College of Food Science, South China Agricultural University, Guangzhou, Guangdong, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Food Science, South China Agricultural University, Guangzhou, Guangdong</wicri:regionArea><wicri:noRegion>Guangdong</wicri:noRegion></affiliation></author><author><name sortKey="Li, Shiming" sort="Li, Shiming" uniqKey="Li S" first="Shiming" last="Li">Shiming Li</name><affiliation wicri:level="1"><nlm:aff id="A4">Department of Food Science, Rutgers, the State University of New Jersey, New Brunswick, NJ, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Food Science, Rutgers, the State University of New Jersey, New Brunswick, NJ</wicri:regionArea><wicri:noRegion>NJ</wicri:noRegion></affiliation></author><author><name sortKey="Ho, Chi Tang" sort="Ho, Chi Tang" uniqKey="Ho C" first="Chi-Tang" last="Ho">Chi-Tang Ho</name><affiliation wicri:level="1"><nlm:aff id="A4">Department of Food Science, Rutgers, the State University of New Jersey, New Brunswick, NJ, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Food Science, Rutgers, the State University of New Jersey, New Brunswick, NJ</wicri:regionArea><wicri:noRegion>NJ</wicri:noRegion></affiliation></author><author><name sortKey="Xiao, Hang" sort="Xiao, Hang" uniqKey="Xiao H" first="Hang" last="Xiao">Hang Xiao</name><affiliation wicri:level="4"><nlm:aff id="A1">Department of Food Science, University of Massachusetts, Amherst, MA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Food Science, University of Massachusetts, Amherst, MA</wicri:regionArea><orgName type="university">Université du Massachusetts</orgName><placeName><settlement type="city">Amherst (Massachusetts)</settlement><region type="state">Massachusetts</region></placeName></affiliation></author></analytic><series><title level="j">Molecular nutrition & food research</title><idno type="ISSN">1613-4125</idno><idno type="eISSN">1613-4133</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Scope</title><p id="P1">Tangeretin and 5-demethyltangeretin (5DT) are two closely related polymethoxyflavones found in citrus fruits. We investigated growth inhibitory effects on three human non-small cell lung cancer (NSCLC) cells.</p></sec><sec id="S2"><title>Methods and results</title><p id="P2">Cell viability assay demonstrated that 5DT inhibited NSCLC cell growth in a time- and dose-dependent manner, and IC<sub>50</sub>s of 5DT were 79-fold, 57-fold and 56-fold lower than those of tangeretin in A549, H460, and H1299 cells, respectively. Flow cytometry analysis showed that 5DT induced extensive G2/M cell cycle arrest and apoptosis in NSCLC cells, while tangeretin at 10-fold higher concentrations did not. The apoptosis induced by 5DT was further confirmed by activation of caspase-3 and cleavage of PARP. Moreover, 5DT dose-dependently upregulated p53 and p21<sup>Cip1/Waf1</sup>, and downregulated Cdc-2 (Cdk-1) and cyclin B1. HPLC analysis revealed that the intracellular levels of 5DT in NSCLC cells were 2.7 - 4.9-fold higher than those of tangeretin after the cells were treated with 5DT or tangeretin at the same concentration.</p></sec><sec id="S3"><title>Conclusions</title><p id="P3">our results demonstrated that 5DT inhibited NSCLC cell growth by inducing G2/M cell cycle arrest and apoptosis. These effects were much stronger than those produced by tangeretin, which is partially due to the higher intracellular uptake of 5DT than tangeretin.</p></sec></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">101231818</journal-id><journal-id journal-id-type="pubmed-jr-id">32150</journal-id><journal-id journal-id-type="nlm-ta">Mol Nutr Food Res</journal-id><journal-id journal-id-type="iso-abbrev">Mol Nutr Food Res</journal-id><journal-title-group><journal-title>Molecular nutrition & food research</journal-title></journal-title-group><issn pub-type="ppub">1613-4125</issn><issn pub-type="epub">1613-4133</issn></journal-meta><article-meta><article-id pub-id-type="pmid">23926120</article-id><article-id pub-id-type="pmc">4648632</article-id><article-id pub-id-type="doi">10.1002/mnfr.201300136</article-id><article-id pub-id-type="manuscript">NIHMS523157</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>5-demethyltangeretin inhibits human non-small cell lung cancer cell growth by inducing G2/M cell cycle arrest and apoptosis</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Charoensinphon</surname><given-names>Noppawat</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Qiu</surname><given-names>Peiju</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Dong</surname><given-names>Ping</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Zheng</surname><given-names>Jinkai</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Ngauv</surname><given-names>Pearline</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Cao</surname><given-names>Yong</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Shiming</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Ho</surname><given-names>Chi-Tang</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Xiao</surname><given-names>Hang</given-names></name><xref ref-type="corresp" rid="CR1">*</xref><xref ref-type="aff" rid="A1">1</xref></contrib></contrib-group><aff id="A1"><label>1</label>Department of Food Science, University of Massachusetts, Amherst, MA, USA</aff><aff id="A2"><label>2</label>Marine Drug and Food Institute, Ocean University of China, Qingdao, Shandong, China</aff><aff id="A3"><label>3</label>College of Food Science, South China Agricultural University, Guangzhou, Guangdong, China</aff><aff id="A4"><label>4</label>Department of Food Science, Rutgers, the State University of New Jersey, New Brunswick, NJ, USA</aff><author-notes><corresp id="CR1"><label>*</label><bold>Corresponding Author:</bold> Hang Xiao, Department of Food Science, University of Massachusetts Amherst, 102 Holdsworth Way, Amherst, MA 01003, USA, Tel: (413) 545-2281; Fax: (413) 545-1262, <email>hangxiao@foodsci.umass.edu</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>13</day><month>11</month><year>2013</year></pub-date><pub-date pub-type="epub"><day>08</day><month>8</month><year>2013</year></pub-date><pub-date pub-type="ppub"><month>12</month><year>2013</year></pub-date><pub-date pub-type="pmc-release"><day>17</day><month>11</month><year>2015</year></pub-date><volume>57</volume><issue>12</issue><fpage>2103</fpage><lpage>2111</lpage><pmc-comment>elocation-id from pubmed: 10.1002/mnfr.201300136</pmc-comment>
<abstract><sec id="S1"><title>Scope</title><p id="P1">Tangeretin and 5-demethyltangeretin (5DT) are two closely related polymethoxyflavones found in citrus fruits. We investigated growth inhibitory effects on three human non-small cell lung cancer (NSCLC) cells.</p></sec><sec id="S2"><title>Methods and results</title><p id="P2">Cell viability assay demonstrated that 5DT inhibited NSCLC cell growth in a time- and dose-dependent manner, and IC<sub>50</sub>s of 5DT were 79-fold, 57-fold and 56-fold lower than those of tangeretin in A549, H460, and H1299 cells, respectively. Flow cytometry analysis showed that 5DT induced extensive G2/M cell cycle arrest and apoptosis in NSCLC cells, while tangeretin at 10-fold higher concentrations did not. The apoptosis induced by 5DT was further confirmed by activation of caspase-3 and cleavage of PARP. Moreover, 5DT dose-dependently upregulated p53 and p21<sup>Cip1/Waf1</sup>, and downregulated Cdc-2 (Cdk-1) and cyclin B1. HPLC analysis revealed that the intracellular levels of 5DT in NSCLC cells were 2.7 - 4.9-fold higher than those of tangeretin after the cells were treated with 5DT or tangeretin at the same concentration.</p></sec><sec id="S3"><title>Conclusions</title><p id="P3">our results demonstrated that 5DT inhibited NSCLC cell growth by inducing G2/M cell cycle arrest and apoptosis. These effects were much stronger than those produced by tangeretin, which is partially due to the higher intracellular uptake of 5DT than tangeretin.</p></sec></abstract><kwd-group><kwd>5-demethyltangeretin</kwd><kwd>5-hydroxy-6,7,8,4′-tetramethoxyflavone</kwd><kwd>apoptosis</kwd><kwd>lung cancer</kwd><kwd>tangeretin</kwd></kwd-group></article-meta></front></pmc><affiliations><list><country><li>République populaire de Chine</li><li>États-Unis</li></country><region><li>Massachusetts</li></region><settlement><li>Amherst (Massachusetts)</li></settlement><orgName><li>Université du Massachusetts</li></orgName></list><tree><country name="États-Unis"><region name="Massachusetts"><name sortKey="Charoensinphon, Noppawat" sort="Charoensinphon, Noppawat" uniqKey="Charoensinphon N" first="Noppawat" last="Charoensinphon">Noppawat Charoensinphon</name></region><name sortKey="Dong, Ping" sort="Dong, Ping" uniqKey="Dong P" first="Ping" last="Dong">Ping Dong</name><name sortKey="Ho, Chi Tang" sort="Ho, Chi Tang" uniqKey="Ho C" first="Chi-Tang" last="Ho">Chi-Tang Ho</name><name sortKey="Li, Shiming" sort="Li, Shiming" uniqKey="Li S" first="Shiming" last="Li">Shiming Li</name><name sortKey="Ngauv, Pearline" sort="Ngauv, Pearline" uniqKey="Ngauv P" first="Pearline" last="Ngauv">Pearline Ngauv</name><name sortKey="Qiu, Peiju" sort="Qiu, Peiju" uniqKey="Qiu P" first="Peiju" last="Qiu">Peiju Qiu</name><name sortKey="Xiao, Hang" sort="Xiao, Hang" uniqKey="Xiao H" first="Hang" last="Xiao">Hang Xiao</name><name sortKey="Zheng, Jinkai" sort="Zheng, Jinkai" uniqKey="Zheng J" first="Jinkai" last="Zheng">Jinkai Zheng</name></country><country name="République populaire de Chine"><noRegion><name sortKey="Qiu, Peiju" sort="Qiu, Peiju" uniqKey="Qiu P" first="Peiju" last="Qiu">Peiju Qiu</name></noRegion><name sortKey="Cao, Yong" sort="Cao, Yong" uniqKey="Cao Y" first="Yong" last="Cao">Yong Cao</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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