Dextran-Catechin inhibits angiogenesis by disrupting copper homeostasis in endothelial cells
Identifieur interne : 000E35 ( Main/Exploration ); précédent : 000E34; suivant : 000E36Dextran-Catechin inhibits angiogenesis by disrupting copper homeostasis in endothelial cells
Auteurs : Eugene M. H. Yee ; Miriam B. Brandl [Australie] ; Eddy Pasquier [Australie, France] ; Giuseppe Cirillo [Italie] ; Kathleen Kimpton [Australie] ; Maria Kavallaris [Australie] ; Naresh Kumar ; Orazio Vittorio [Australie]Source :
- Scientific Reports [ 2045-2322 ] ; 2017.
Abstract
Formation of blood vessels, or angiogenesis, is crucial to cancer progression. Thus, inhibiting angiogenesis can limit the growth and spread of tumors. The natural polyphenol catechin has moderate anti-tumor activity and interacts with copper, which is essential for angiogenesis. Catechin is easily metabolized in the body and this limits its clinical application. We have recently shown that conjugation of catechin with dextran (Dextran-Catechin) improves its serum stability, and exhibits potent anti-tumor activity against neuroblastoma by targeting copper homeostasis. Herein, we investigated the antiangiogenic activity of Dextran-Catechin and its mechanism. We found that Dextran-Catechin displayed potent antiangiogenic activity
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DOI: 10.1038/s41598-017-07452-w
PubMed: 28794411
PubMed Central: 5550437
Affiliations:
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0432</institution-id><institution-id institution-id-type="GRID">grid.1005.4</institution-id><institution>School of Chemistry,</institution><institution>UNSW Australia,</institution></institution-wrap>Sydney, NSW 2052 Australia</nlm:aff><wicri:noCountry code="subfield">NSW 2052 Australia</wicri:noCountry></affiliation></author><author><name sortKey="Vittorio, Orazio" sort="Vittorio, Orazio" uniqKey="Vittorio O" first="Orazio" last="Vittorio">Orazio Vittorio</name><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 4902 0432</institution-id><institution-id institution-id-type="GRID">grid.1005.4</institution-id><institution>Children’s Cancer Institute, Lowy Cancer Research Centre,</institution><institution>University of New South Wales,</institution></institution-wrap>Sydney, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Sydney</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 4902 0432</institution-id><institution-id institution-id-type="GRID">grid.1005.4</institution-id><institution>Australian Centre for NanoMedicine, ARC Centre of Excellence in Convergent Bio-Nano Science and Technology,</institution><institution>University of New South Wales,</institution></institution-wrap>NSW Sydney, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>NSW Sydney</wicri:regionArea></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">Formation of blood vessels, or angiogenesis, is crucial to cancer progression. Thus, inhibiting angiogenesis can limit the growth and spread of tumors. The natural polyphenol catechin has moderate anti-tumor activity and interacts with copper, which is essential for angiogenesis. Catechin is easily metabolized in the body and this limits its clinical application. We have recently shown that conjugation of catechin with dextran (Dextran-Catechin) improves its serum stability, and exhibits potent anti-tumor activity against neuroblastoma by targeting copper homeostasis. Herein, we investigated the antiangiogenic activity of Dextran-Catechin and its mechanism. We found that Dextran-Catechin displayed potent antiangiogenic activity <italic>in vitro</italic> and <italic>in vivo</italic>. We demonstrated Dextran-Catechin generates reactive oxygen species which in turns disrupts copper homeostasis by depleting the copper importer CTR-1 and copper trafficking ATOX-1 protein. Mechanistically, we showed that disrupting copper homeostasis by knockdown of either CTR-1 or ATOX-1 protein can inhibit angiogenesis in endothelial cells. This data strongly suggests the Dextran-Catechin potent antiangiogenic activity is mediated by disrupting copper homeostasis. Thus, compounds such as Dextran-Catechin that affects both tumor growth and angiogenesis could lead the way for development of new drugs against high copper levels tumors.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Sitohy, B" uniqKey="Sitohy B">B Sitohy</name></author><author><name sortKey="Nagy, Ja" uniqKey="Nagy J">JA Nagy</name></author><author><name sortKey="Dvorak, Hf" uniqKey="Dvorak H">HF Dvorak</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vasudev, Ns" uniqKey="Vasudev N">NS Vasudev</name></author><author><name sortKey="Reynolds, Ar" uniqKey="Reynolds A">AR Reynolds</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jain, Rk" uniqKey="Jain R">RK Jain</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Browder, T" uniqKey="Browder T">T Browder</name></author></analytic></biblStruct><biblStruct><analytic><author><name 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Howell</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Australie</li><li>France</li><li>Italie</li></country></list><tree><noCountry><name sortKey="Kumar, Naresh" sort="Kumar, Naresh" uniqKey="Kumar N" first="Naresh" last="Kumar">Naresh Kumar</name><name sortKey="Yee, Eugene M H" sort="Yee, Eugene M H" uniqKey="Yee E" first="Eugene M. H." last="Yee">Eugene M. H. Yee</name></noCountry><country name="Australie"><noRegion><name sortKey="Brandl, Miriam B" sort="Brandl, Miriam B" uniqKey="Brandl M" first="Miriam B." last="Brandl">Miriam B. Brandl</name></noRegion><name sortKey="Brandl, Miriam B" sort="Brandl, Miriam B" uniqKey="Brandl M" first="Miriam B." last="Brandl">Miriam B. Brandl</name><name sortKey="Kavallaris, Maria" sort="Kavallaris, Maria" uniqKey="Kavallaris M" first="Maria" last="Kavallaris">Maria Kavallaris</name><name sortKey="Kavallaris, Maria" sort="Kavallaris, Maria" uniqKey="Kavallaris M" first="Maria" last="Kavallaris">Maria Kavallaris</name><name sortKey="Kimpton, Kathleen" sort="Kimpton, Kathleen" uniqKey="Kimpton K" first="Kathleen" last="Kimpton">Kathleen Kimpton</name><name sortKey="Pasquier, Eddy" sort="Pasquier, Eddy" uniqKey="Pasquier E" first="Eddy" last="Pasquier">Eddy Pasquier</name><name sortKey="Vittorio, Orazio" sort="Vittorio, Orazio" uniqKey="Vittorio O" first="Orazio" last="Vittorio">Orazio Vittorio</name><name sortKey="Vittorio, Orazio" sort="Vittorio, Orazio" uniqKey="Vittorio O" first="Orazio" last="Vittorio">Orazio Vittorio</name></country><country name="France"><noRegion><name sortKey="Pasquier, Eddy" sort="Pasquier, Eddy" uniqKey="Pasquier E" first="Eddy" last="Pasquier">Eddy Pasquier</name></noRegion></country><country name="Italie"><noRegion><name sortKey="Cirillo, Giuseppe" sort="Cirillo, Giuseppe" uniqKey="Cirillo G" first="Giuseppe" last="Cirillo">Giuseppe Cirillo</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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