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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Potent and broad anticancer activities of leaf extracts from <italic>Melia azedarach</italic> L. of the subtropical Okinawa islands</title><author><name sortKey="Nerome, Kuniaki" sort="Nerome, Kuniaki" uniqKey="Nerome K" first="Kuniaki" last="Nerome">Kuniaki Nerome</name><affiliation><nlm:aff id="au1"><institution>The Institute of Biological Resources</institution><addr-line>893-2, Nakayama, Nago-shi, Okinawa 905-0004, Japan</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ito Kureha, Taku" sort="Ito Kureha, Taku" uniqKey="Ito Kureha T" first="Taku" last="Ito-Kureha">Taku Ito-Kureha</name><affiliation><nlm:aff id="au2"><institution>Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University</institution><addr-line>Onna, Okinawa 904-0495, Japan</addr-line></nlm:aff></affiliation></author><author><name sortKey="Paganini, Tiziana" sort="Paganini, Tiziana" uniqKey="Paganini T" first="Tiziana" last="Paganini">Tiziana Paganini</name><affiliation><nlm:aff id="au2"><institution>Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University</institution><addr-line>Onna, Okinawa 904-0495, Japan</addr-line></nlm:aff></affiliation></author><author><name sortKey="Fukuda, Takao" sort="Fukuda, Takao" uniqKey="Fukuda T" first="Takao" last="Fukuda">Takao Fukuda</name><affiliation><nlm:aff id="au3"><institution>Biotechnology Research Center and Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University</institution><addr-line>5180 Kurokawa, Imizu, Toyama 939-0398, Japan</addr-line></nlm:aff></affiliation></author><author><name sortKey="Igarashi, Yasuhiro" sort="Igarashi, Yasuhiro" uniqKey="Igarashi Y" first="Yasuhiro" last="Igarashi">Yasuhiro Igarashi</name><affiliation><nlm:aff id="au3"><institution>Biotechnology Research Center and Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University</institution><addr-line>5180 Kurokawa, Imizu, Toyama 939-0398, Japan</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ashitomi, Hiroto" sort="Ashitomi, Hiroto" uniqKey="Ashitomi H" first="Hiroto" last="Ashitomi">Hiroto Ashitomi</name><affiliation><nlm:aff id="au4"><institution>National Institute of Technology, Okinawa College</institution><addr-line>Henoko 905, Nago-shi, Okinawa 905-2192, Japan</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ikematsu, Shinya" sort="Ikematsu, Shinya" uniqKey="Ikematsu S" first="Shinya" last="Ikematsu">Shinya Ikematsu</name><affiliation><nlm:aff id="au4"><institution>National Institute of Technology, Okinawa College</institution><addr-line>Henoko 905, Nago-shi, Okinawa 905-2192, Japan</addr-line></nlm:aff></affiliation></author><author><name sortKey="Yamamoto, Tadashi" sort="Yamamoto, Tadashi" uniqKey="Yamamoto T" first="Tadashi" last="Yamamoto">Tadashi Yamamoto</name><affiliation><nlm:aff id="au2"><institution>Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University</institution><addr-line>Onna, Okinawa 904-0495, Japan</addr-line></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32195029</idno><idno type="pmc">7061759</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061759</idno><idno type="RBID">PMC:7061759</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000349</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000349</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Potent and broad anticancer activities of leaf extracts from <italic>Melia azedarach</italic> L. of the subtropical Okinawa islands</title><author><name sortKey="Nerome, Kuniaki" sort="Nerome, Kuniaki" uniqKey="Nerome K" first="Kuniaki" last="Nerome">Kuniaki Nerome</name><affiliation><nlm:aff id="au1"><institution>The Institute of Biological Resources</institution><addr-line>893-2, Nakayama, Nago-shi, Okinawa 905-0004, Japan</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ito Kureha, Taku" sort="Ito Kureha, Taku" uniqKey="Ito Kureha T" first="Taku" last="Ito-Kureha">Taku Ito-Kureha</name><affiliation><nlm:aff id="au2"><institution>Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University</institution><addr-line>Onna, Okinawa 904-0495, Japan</addr-line></nlm:aff></affiliation></author><author><name sortKey="Paganini, Tiziana" sort="Paganini, Tiziana" uniqKey="Paganini T" first="Tiziana" last="Paganini">Tiziana Paganini</name><affiliation><nlm:aff id="au2"><institution>Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University</institution><addr-line>Onna, Okinawa 904-0495, Japan</addr-line></nlm:aff></affiliation></author><author><name sortKey="Fukuda, Takao" sort="Fukuda, Takao" uniqKey="Fukuda T" first="Takao" last="Fukuda">Takao Fukuda</name><affiliation><nlm:aff id="au3"><institution>Biotechnology Research Center and Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University</institution><addr-line>5180 Kurokawa, Imizu, Toyama 939-0398, Japan</addr-line></nlm:aff></affiliation></author><author><name sortKey="Igarashi, Yasuhiro" sort="Igarashi, Yasuhiro" uniqKey="Igarashi Y" first="Yasuhiro" last="Igarashi">Yasuhiro Igarashi</name><affiliation><nlm:aff id="au3"><institution>Biotechnology Research Center and Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University</institution><addr-line>5180 Kurokawa, Imizu, Toyama 939-0398, Japan</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ashitomi, Hiroto" sort="Ashitomi, Hiroto" uniqKey="Ashitomi H" first="Hiroto" last="Ashitomi">Hiroto Ashitomi</name><affiliation><nlm:aff id="au4"><institution>National Institute of Technology, Okinawa College</institution><addr-line>Henoko 905, Nago-shi, Okinawa 905-2192, Japan</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ikematsu, Shinya" sort="Ikematsu, Shinya" uniqKey="Ikematsu S" first="Shinya" last="Ikematsu">Shinya Ikematsu</name><affiliation><nlm:aff id="au4"><institution>National Institute of Technology, Okinawa College</institution><addr-line>Henoko 905, Nago-shi, Okinawa 905-2192, Japan</addr-line></nlm:aff></affiliation></author><author><name sortKey="Yamamoto, Tadashi" sort="Yamamoto, Tadashi" uniqKey="Yamamoto T" first="Tadashi" last="Yamamoto">Tadashi Yamamoto</name><affiliation><nlm:aff id="au2"><institution>Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University</institution><addr-line>Onna, Okinawa 904-0495, Japan</addr-line></nlm:aff></affiliation></author></analytic><series><title level="j">American Journal of Cancer Research</title><idno type="eISSN">2156-6976</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Plant extracts have been traditionally used for various therapeutic applications. By conducting an initial screening of several subtropical plants, in this study, we evaluated the anticancer activities of <italic>Melia azedarach L</italic>. The extract from <italic>Melia azedarach L</italic>. leaves (MLE) show high cytotoxic effects on cancer cells and <italic>in vivo</italic> mouse and dog tumor models. During the initial screening, MLE showed strong antiproliferative activity against HT-29 colon, A549 lung, and MKN1 gastric cancer cells. In subsequent tests, using 39 human tumor cell lines, we confirmed the potent anticancer activities of MLE. The anticancer activity of MLE was also confirmed <italic>in vivo</italic>. MLE markedly inhibited the growth of transplanted gastric MKN1 cancer xenografts in mice. To elucidate the mechanism underlying the anticancer effects of MLE, MLE-treated MKN1 cells were observed using an electron microscope; MLE treatment induced autophagy. Furthermore, western blot analysis of proteins in lysates of MLE-treated cells revealed induction of light chain 3 (LC3)-II autophagosomal proteins. Thus, MLE appeared to suppress MKN1 cell proliferation by inducing autophagy. In addition, in the mouse macrophage cell line J774A.1, MLE treatment induced TNF-α production, which might play a role in tumor growth suppression <italic>in vivo</italic>. We also performed a preclinical evaluation of MLE treatment on dogs with various cancers in veterinary hospitals. Dogs with various types of cancers showed a mean recovery of 76% when treated with MLE. Finally, we tried to identify the active substances present in MLE. All the active fractions obtained by reverse-phase chromatography contained azedarachin B-related moieties, such as 3-deacetyl-12-hydroxy-amoorastatin, 12-hydroxy-amoorastatin, and 12-hydroxyamoorastaton. In conclusion, MLE contains substances with promising anticancer effects, suggesting their future use as safe and effective anticancer agents.</p></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>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Am J Cancer Res</journal-id><journal-id journal-id-type="iso-abbrev">Am J Cancer Res</journal-id><journal-id journal-id-type="publisher-id">ajcr</journal-id><journal-title-group><journal-title>American Journal of Cancer Research</journal-title></journal-title-group><issn pub-type="epub">2156-6976</issn><publisher><publisher-name>e-Century Publishing Corporation</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32195029</article-id><article-id pub-id-type="pmc">7061759</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Article</subject></subj-group></article-categories><title-group><article-title>Potent and broad anticancer activities of leaf extracts from <italic>Melia azedarach</italic> L. of the subtropical Okinawa islands</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Nerome</surname><given-names>Kuniaki</given-names></name><xref ref-type="aff" rid="au1">1</xref></contrib><contrib contrib-type="author"><name><surname>Ito-Kureha</surname><given-names>Taku</given-names></name><xref ref-type="aff" rid="au2">2</xref></contrib><contrib contrib-type="author"><name><surname>Paganini</surname><given-names>Tiziana</given-names></name><xref ref-type="aff" rid="au2">2</xref></contrib><contrib contrib-type="author"><name><surname>Fukuda</surname><given-names>Takao</given-names></name><xref ref-type="aff" rid="au3">3</xref></contrib><contrib contrib-type="author"><name><surname>Igarashi</surname><given-names>Yasuhiro</given-names></name><xref ref-type="aff" rid="au3">3</xref></contrib><contrib contrib-type="author"><name><surname>Ashitomi</surname><given-names>Hiroto</given-names></name><xref ref-type="aff" rid="au4">4</xref></contrib><contrib contrib-type="author"><name><surname>Ikematsu</surname><given-names>Shinya</given-names></name><xref ref-type="aff" rid="au4">4</xref></contrib><contrib contrib-type="author"><name><surname>Yamamoto</surname><given-names>Tadashi</given-names></name><xref ref-type="aff" rid="au2">2</xref></contrib><aff id="au1"><label>1</label><institution>The Institute of Biological Resources</institution><addr-line>893-2, Nakayama, Nago-shi, Okinawa 905-0004, Japan</addr-line></aff><aff id="au2"><label>2</label><institution>Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University</institution><addr-line>Onna, Okinawa 904-0495, Japan</addr-line></aff><aff id="au3"><label>3</label><institution>Biotechnology Research Center and Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University</institution><addr-line>5180 Kurokawa, Imizu, Toyama 939-0398, Japan</addr-line></aff><aff id="au4"><label>4</label><institution>National Institute of Technology, Okinawa College</institution><addr-line>Henoko 905, Nago-shi, Okinawa 905-2192, Japan</addr-line></aff></contrib-group><author-notes><corresp><bold>Address correspondence to:</bold> Dr. Kuniaki Nerome, The Institute of Biological Resources, 893-2, Nakayama, Nago City, Okinawa 905-0004, Japan. Tel: +81-980-54-3376; Fax: +81-980-54-3457; E-mail: <email>rnerome_ibr@train.ocn.ne.jp</email></corresp></author-notes><pub-date pub-type="collection"><year>2020</year></pub-date><pub-date pub-type="epub"><day>01</day><month>2</month><year>2020</year></pub-date><volume>10</volume><issue>2</issue><fpage>581</fpage><lpage>594</lpage><history><date date-type="received"><day>06</day><month>8</month><year>2019</year></date><date date-type="accepted"><day>23</day><month>1</month><year>2020</year></date></history><permissions><copyright-statement>AJCR Copyright © 2020</copyright-statement><copyright-year>2020</copyright-year></permissions><abstract><p>Plant extracts have been traditionally used for various therapeutic applications. By conducting an initial screening of several subtropical plants, in this study, we evaluated the anticancer activities of <italic>Melia azedarach L</italic>. The extract from <italic>Melia azedarach L</italic>. leaves (MLE) show high cytotoxic effects on cancer cells and <italic>in vivo</italic> mouse and dog tumor models. During the initial screening, MLE showed strong antiproliferative activity against HT-29 colon, A549 lung, and MKN1 gastric cancer cells. In subsequent tests, using 39 human tumor cell lines, we confirmed the potent anticancer activities of MLE. The anticancer activity of MLE was also confirmed <italic>in vivo</italic>. MLE markedly inhibited the growth of transplanted gastric MKN1 cancer xenografts in mice. To elucidate the mechanism underlying the anticancer effects of MLE, MLE-treated MKN1 cells were observed using an electron microscope; MLE treatment induced autophagy. Furthermore, western blot analysis of proteins in lysates of MLE-treated cells revealed induction of light chain 3 (LC3)-II autophagosomal proteins. Thus, MLE appeared to suppress MKN1 cell proliferation by inducing autophagy. In addition, in the mouse macrophage cell line J774A.1, MLE treatment induced TNF-α production, which might play a role in tumor growth suppression <italic>in vivo</italic>. We also performed a preclinical evaluation of MLE treatment on dogs with various cancers in veterinary hospitals. Dogs with various types of cancers showed a mean recovery of 76% when treated with MLE. Finally, we tried to identify the active substances present in MLE. All the active fractions obtained by reverse-phase chromatography contained azedarachin B-related moieties, such as 3-deacetyl-12-hydroxy-amoorastatin, 12-hydroxy-amoorastatin, and 12-hydroxyamoorastaton. In conclusion, MLE contains substances with promising anticancer effects, suggesting their future use as safe and effective anticancer agents.</p></abstract><kwd-group><kwd>Cancer</kwd><kwd>anticancer therapeutics</kwd><kwd>plant extracts</kwd><kwd><italic>Melia azedarach</italic></kwd><kwd>autophagy inhibitors</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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