Monodemethylated polymethoxyflavones from sweet orange (Citrus sinensis) peel inhibit growth of human lung cancer cells by apoptosis
Identifieur interne : 001F41 ( Main/Exploration ); précédent : 001F40; suivant : 001F42Monodemethylated polymethoxyflavones from sweet orange (Citrus sinensis) peel inhibit growth of human lung cancer cells by apoptosis
Auteurs : HANG XIAO [États-Unis] ; Chung S. Yang [États-Unis] ; SHIMING LI [États-Unis] ; HUANYU JIN [États-Unis] ; Chi-Tang Ho [États-Unis] ; Trusha Patel [États-Unis]Source :
- Molecular nutrition & food research : (Print) [ 1613-4125 ] ; 2009.
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- topic : Homme.
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Abstract
Polymethoxyflavones (PMFs) are almost exclusively found in the Citrus genus, particularly in the peels of sweet orange (Citrus sinensis L. Osbeck) and mandarin (C. reticulate Blanco). We studied the effects of two major PMFs, namely, nobiletin and 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF), and two major monodemethylated PMFs, namely 5-hydroxy-3,7,8,3',4'-pentamethoxyflavone (5HPMF), and 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone (5HHMF), on the growth of human lung cancer H1299, H441, and H460 cells. Monodemethylated PMFs were much more potent in growth inhibition of lung cancer cells than their permethoxylated counterpart PMFs. In H1299 cells, cell cycle analyses further revealed that monodemethylated PMFs caused significant increase in sub-G0/ Gl phase, suggesting possible role of apoptosis in the growth inhibition observed, whereas the permethoxylated counterpart PMFs did not affect cell cycle distribution at same concentrations tested. These results strongly suggested that the phenolic group is essential for the growth inhibitory activity of monodemethylated PMFs. Further studies in H1299 cells demonstrated that monodemethylated PMFs downregulated oncogenic proteins, such as iNOS, COX-2, Mcl-1, and K-ras, as well as induced apoptosis evidenced by activation of caspase-3 and cleavage of PARP. Our results provide rationale to develop orange peel extract enriched with monodemethylated PMFs into value-added nutraceutical products for cancer prevention.
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Yang</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey</s1><s2>Piscataway, NJ</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">New Jersey</region></placeName></affiliation></author><author><name sortKey="Shiming Li" sort="Shiming Li" uniqKey="Shiming Li" last="Shiming Li">SHIMING LI</name><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>WellGen, Inc</s1><s2>North Brunswick, NJ</s2><s3>USA</s3><sZ>3 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">New Jersey</region></placeName></affiliation></author><author><name sortKey="Huanyu Jin" sort="Huanyu Jin" uniqKey="Huanyu Jin" last="Huanyu Jin">HUANYU JIN</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey</s1><s2>Piscataway, NJ</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">New Jersey</region></placeName></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="2"><inist:fA14 i1="04"><s1>Department of Food Science, Rutgers, The State University of New Jersey</s1><s2>New Brunswick, NJ</s2><s3>USA</s3><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">New Jersey</region></placeName></affiliation></author><author><name sortKey="Patel, Trusha" sort="Patel, Trusha" uniqKey="Patel T" first="Trusha" last="Patel">Trusha Patel</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey</s1><s2>Piscataway, NJ</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">New Jersey</region></placeName></affiliation></author></analytic><series><title level="j" type="main">Molecular nutrition & food research : (Print)</title><title level="j" type="abbreviated">Mol. nutr. food res. : (Print)</title><idno type="ISSN">1613-4125</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Molecular nutrition & food research : (Print)</title><title level="j" type="abbreviated">Mol. nutr. food res. : (Print)</title><idno type="ISSN">1613-4125</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Citrus sinensis</term><term>Growth</term><term>Human</term><term>Malignant tumor</term><term>Orange</term><term>Peel</term><term>Sweets</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Bonbon</term><term>Orange</term><term>Citrus sinensis</term><term>Pelure</term><term>Croissance</term><term>Homme</term><term>Tumeur maligne</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Polymethoxyflavones (PMFs) are almost exclusively found in the Citrus genus, particularly in the peels of sweet orange (Citrus sinensis L. Osbeck) and mandarin (C. reticulate Blanco). We studied the effects of two major PMFs, namely, nobiletin and 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF), and two major monodemethylated PMFs, namely 5-hydroxy-3,7,8,3',4'-pentamethoxyflavone (5HPMF), and 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone (5HHMF), on the growth of human lung cancer H1299, H441, and H460 cells. Monodemethylated PMFs were much more potent in growth inhibition of lung cancer cells than their permethoxylated counterpart PMFs. In H1299 cells, cell cycle analyses further revealed that monodemethylated PMFs caused significant increase in sub-G0/ Gl phase, suggesting possible role of apoptosis in the growth inhibition observed, whereas the permethoxylated counterpart PMFs did not affect cell cycle distribution at same concentrations tested. These results strongly suggested that the phenolic group is essential for the growth inhibitory activity of monodemethylated PMFs. Further studies in H1299 cells demonstrated that monodemethylated PMFs downregulated oncogenic proteins, such as iNOS, COX-2, Mcl-1, and K-ras, as well as induced apoptosis evidenced by activation of caspase-3 and cleavage of PARP. Our results provide rationale to develop orange peel extract enriched with monodemethylated PMFs into value-added nutraceutical products for cancer prevention.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Massachusetts</li><li>New Jersey</li></region><settlement><li>Amherst (Massachusetts)</li></settlement><orgName><li>Université du Massachusetts</li></orgName></list><tree><country name="États-Unis"><region name="New Jersey"><name sortKey="Hang Xiao" sort="Hang Xiao" uniqKey="Hang Xiao" last="Hang Xiao">HANG XIAO</name></region><name sortKey="Hang Xiao" sort="Hang Xiao" uniqKey="Hang Xiao" last="Hang Xiao">HANG XIAO</name><name sortKey="Ho, Chi Tang" sort="Ho, Chi Tang" uniqKey="Ho C" first="Chi-Tang" last="Ho">Chi-Tang Ho</name><name sortKey="Huanyu Jin" sort="Huanyu Jin" uniqKey="Huanyu Jin" last="Huanyu Jin">HUANYU JIN</name><name sortKey="Patel, Trusha" sort="Patel, Trusha" uniqKey="Patel T" first="Trusha" last="Patel">Trusha Patel</name><name sortKey="Shiming Li" sort="Shiming Li" uniqKey="Shiming Li" last="Shiming Li">SHIMING LI</name><name sortKey="Yang, Chung S" sort="Yang, Chung S" uniqKey="Yang C" first="Chung S." last="Yang">Chung S. 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