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<record>
<TEI>
<teiHeader>
<fileDesc>
<titleStmt>
<title xml:lang="en">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>
<nlm:aff id="A1">Department of Food Science, University of Massachusetts, Amherst, MA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Qiu, Peiju" sort="Qiu, Peiju" uniqKey="Qiu P" first="Peiju" last="Qiu">Peiju Qiu</name>
<affiliation>
<nlm:aff id="A1">Department of Food Science, University of Massachusetts, Amherst, MA, USA</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A2">Marine Drug and Food Institute, Ocean University of China, Qingdao, Shandong, China</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Dong, Ping" sort="Dong, Ping" uniqKey="Dong P" first="Ping" last="Dong">Ping Dong</name>
<affiliation>
<nlm:aff id="A1">Department of Food Science, University of Massachusetts, Amherst, MA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Zheng, Jinkai" sort="Zheng, Jinkai" uniqKey="Zheng J" first="Jinkai" last="Zheng">Jinkai Zheng</name>
<affiliation>
<nlm:aff id="A1">Department of Food Science, University of Massachusetts, Amherst, MA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Ngauv, Pearline" sort="Ngauv, Pearline" uniqKey="Ngauv P" first="Pearline" last="Ngauv">Pearline Ngauv</name>
<affiliation>
<nlm:aff id="A1">Department of Food Science, University of Massachusetts, Amherst, MA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Cao, Yong" sort="Cao, Yong" uniqKey="Cao Y" first="Yong" last="Cao">Yong Cao</name>
<affiliation>
<nlm:aff id="A3">College of Food Science, South China Agricultural University, Guangzhou, Guangdong, China</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Li, Shiming" sort="Li, Shiming" uniqKey="Li S" first="Shiming" last="Li">Shiming Li</name>
<affiliation>
<nlm:aff id="A4">Department of Food Science, Rutgers, the State University of New Jersey, New Brunswick, NJ, USA</nlm:aff>
</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>
<nlm:aff id="A4">Department of Food Science, Rutgers, the State University of New Jersey, New Brunswick, NJ, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Xiao, Hang" sort="Xiao, Hang" uniqKey="Xiao H" first="Hang" last="Xiao">Hang Xiao</name>
<affiliation>
<nlm:aff id="A1">Department of Food Science, University of Massachusetts, Amherst, MA, USA</nlm:aff>
</affiliation>
</author>
</titleStmt>
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<idno type="wicri:source">PMC</idno>
<idno type="pmid">23926120</idno>
<idno type="pmc">4648632</idno>
<idno 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>
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<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>
<nlm:aff id="A1">Department of Food Science, University of Massachusetts, Amherst, MA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Qiu, Peiju" sort="Qiu, Peiju" uniqKey="Qiu P" first="Peiju" last="Qiu">Peiju Qiu</name>
<affiliation>
<nlm:aff id="A1">Department of Food Science, University of Massachusetts, Amherst, MA, USA</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A2">Marine Drug and Food Institute, Ocean University of China, Qingdao, Shandong, China</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Dong, Ping" sort="Dong, Ping" uniqKey="Dong P" first="Ping" last="Dong">Ping Dong</name>
<affiliation>
<nlm:aff id="A1">Department of Food Science, University of Massachusetts, Amherst, MA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Zheng, Jinkai" sort="Zheng, Jinkai" uniqKey="Zheng J" first="Jinkai" last="Zheng">Jinkai Zheng</name>
<affiliation>
<nlm:aff id="A1">Department of Food Science, University of Massachusetts, Amherst, MA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Ngauv, Pearline" sort="Ngauv, Pearline" uniqKey="Ngauv P" first="Pearline" last="Ngauv">Pearline Ngauv</name>
<affiliation>
<nlm:aff id="A1">Department of Food Science, University of Massachusetts, Amherst, MA, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Cao, Yong" sort="Cao, Yong" uniqKey="Cao Y" first="Yong" last="Cao">Yong Cao</name>
<affiliation>
<nlm:aff id="A3">College of Food Science, South China Agricultural University, Guangzhou, Guangdong, China</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Li, Shiming" sort="Li, Shiming" uniqKey="Li S" first="Shiming" last="Li">Shiming Li</name>
<affiliation>
<nlm:aff id="A4">Department of Food Science, Rutgers, the State University of New Jersey, New Brunswick, NJ, USA</nlm:aff>
</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>
<nlm:aff id="A4">Department of Food Science, Rutgers, the State University of New Jersey, New Brunswick, NJ, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Xiao, Hang" sort="Xiao, Hang" uniqKey="Xiao H" first="Hang" last="Xiao">Hang Xiao</name>
<affiliation>
<nlm:aff id="A1">Department of Food Science, University of Massachusetts, Amherst, MA, USA</nlm:aff>
</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>
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<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>
</record>

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