The fungicide ciclopirox inhibits lymphatic endothelial cell tube formation by suppressing VEGFR-3-mediated ERK signaling pathway
Identifieur interne : 000275 ( France/Analysis ); précédent : 000274; suivant : 000276The fungicide ciclopirox inhibits lymphatic endothelial cell tube formation by suppressing VEGFR-3-mediated ERK signaling pathway
Auteurs : Yan Luo [États-Unis, République populaire de Chine] ; Hongyu Zhou [États-Unis] ; Lei Liu [États-Unis] ; Tao Shen [États-Unis] ; Wenxing Chen [États-Unis] ; Baoshan Xu [États-Unis] ; Xiuzhen Han [États-Unis] ; Fangfang Zhang [États-Unis] ; Rona S. Scott [États-Unis] ; J. Steven Alexander [États-Unis] ; Antoine Alam [France] ; Shile Huang [États-Unis]Source :
- Oncogene [ 0950-9232 ] ; 2011.
Abstract
Ciclopirox olamine (CPX), an off-patent antifungal agent used to treat mycoses of skin and nails, has recently been demonstrated to be a potential anticancer agent. However, the underlying mechanism is not well understood. Here for the first time we show that CPX inhibited lymphangiogenesis in an
Url:
DOI: 10.1038/onc.2010.590
PubMed: 21217783
PubMed Central: 3088775
Affiliations:
- France, République populaire de Chine, États-Unis
- Midi-Pyrénées, Occitanie (région administrative)
- Toulouse
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Health Sciences Center, Shreveport, LA 71130-3932</wicri:regionArea><wicri:noRegion>LA 71130-3932</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A6"> State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People’s Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea> State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041</wicri:regionArea><wicri:noRegion>Sichuan 610041</wicri:noRegion></affiliation></author><author><name sortKey="Zhou, Hongyu" sort="Zhou, Hongyu" uniqKey="Zhou H" first="Hongyu" last="Zhou">Hongyu Zhou</name><affiliation wicri:level="1"><nlm:aff id="A1"> Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932</wicri:regionArea><wicri:noRegion>LA 71130-3932</wicri:noRegion></affiliation></author><author><name sortKey="Liu, Lei" sort="Liu, Lei" uniqKey="Liu L" first="Lei" last="Liu">Lei Liu</name><affiliation wicri:level="1"><nlm:aff id="A1"> Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932</wicri:regionArea><wicri:noRegion>LA 71130-3932</wicri:noRegion></affiliation></author><author><name sortKey="Shen, Tao" sort="Shen, Tao" uniqKey="Shen T" first="Tao" last="Shen">Tao Shen</name><affiliation wicri:level="1"><nlm:aff id="A1"> Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932</wicri:regionArea><wicri:noRegion>LA 71130-3932</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Wenxing" sort="Chen, Wenxing" uniqKey="Chen W" first="Wenxing" last="Chen">Wenxing Chen</name><affiliation wicri:level="1"><nlm:aff id="A1"> Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932</wicri:regionArea><wicri:noRegion>LA 71130-3932</wicri:noRegion></affiliation></author><author><name sortKey="Xu, Baoshan" sort="Xu, Baoshan" uniqKey="Xu B" first="Baoshan" last="Xu">Baoshan Xu</name><affiliation wicri:level="1"><nlm:aff id="A1"> Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932</wicri:regionArea><wicri:noRegion>LA 71130-3932</wicri:noRegion></affiliation></author><author><name sortKey="Han, Xiuzhen" sort="Han, Xiuzhen" uniqKey="Han X" first="Xiuzhen" last="Han">Xiuzhen Han</name><affiliation wicri:level="1"><nlm:aff id="A1"> Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932</wicri:regionArea><wicri:noRegion>LA 71130-3932</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Fangfang" sort="Zhang, Fangfang" uniqKey="Zhang F" first="Fangfang" last="Zhang">Fangfang Zhang</name><affiliation wicri:level="1"><nlm:aff id="A2"> Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932</wicri:regionArea><wicri:noRegion>LA 71130-3932</wicri:noRegion></affiliation></author><author><name sortKey="Scott, Rona S" sort="Scott, Rona S" uniqKey="Scott R" first="Rona S." last="Scott">Rona S. Scott</name><affiliation wicri:level="1"><nlm:aff id="A2"> Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932</wicri:regionArea><wicri:noRegion>LA 71130-3932</wicri:noRegion></affiliation></author><author><name sortKey="Alexander, J Steven" sort="Alexander, J Steven" uniqKey="Alexander J" first="J. Steven" last="Alexander">J. Steven Alexander</name><affiliation wicri:level="1"><nlm:aff id="A3"> Deoartement of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Deoartement of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932</wicri:regionArea><wicri:noRegion>LA 71130-3932</wicri:noRegion></affiliation></author><author><name sortKey="Alam, Antoine" sort="Alam, Antoine" uniqKey="Alam A" first="Antoine" last="Alam">Antoine Alam</name><affiliation wicri:level="1"><nlm:aff id="A5"> Sanofi-Aventis R&D, 31036 Toulouse, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea> Sanofi-Aventis R&D, 31036 Toulouse</wicri:regionArea><wicri:noRegion>31036 Toulouse</wicri:noRegion><placeName><settlement type="city">Toulouse</settlement><region type="region" nuts="2">Occitanie (région administrative)</region><region type="old region" nuts="2">Midi-Pyrénées</region></placeName></affiliation></author><author><name sortKey="Huang, Shile" sort="Huang, Shile" uniqKey="Huang S" first="Shile" last="Huang">Shile Huang</name><affiliation wicri:level="1"><nlm:aff id="A1"> Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932</wicri:regionArea><wicri:noRegion>LA 71130-3932</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="A4"> Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea> Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932</wicri:regionArea><wicri:noRegion>LA 71130-3932</wicri:noRegion></affiliation></author></analytic><series><title level="j">Oncogene</title><idno type="ISSN">0950-9232</idno><idno type="eISSN">1476-5594</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Ciclopirox olamine (CPX), an off-patent antifungal agent used to treat mycoses of skin and nails, has recently been demonstrated to be a potential anticancer agent. However, the underlying mechanism is not well understood. Here for the first time we show that CPX inhibited lymphangiogenesis in an <italic>in vitro</italic> model (tube formation). This effect was in part associated with inhibition of vascular endothelial growth factor receptor 3 (VEGFR-3) expression, as overexpression of VEGFR-3 conferred partial resistance to CPX inhibitory effect on tube formation in <underline>lymphatic endothelial cells</underline> (LECs), whereas downregulation of VEGFR-3 mimicked the effect of CPX, blocking the tube formation. Further study revealed that CPX did not alter mRNA level, but inhibited protein synthesis and promoted protein degradation of VEGFR-3. In addition, we found that CPX inhibited phosphorylation of the extracellular signal-related kinase 1/2 (ERK1/2), a downstream effector of VEGFR-3. Overexpression of VEGFR-3 attenuated CPX inhibition of ERK1/2 phosphorylation, whereas downregulation of VEGFR-3 inhibited <underline>extracellular signal-related kinase 1/2 (ERK1/2)</underline> phosphorylation in LECs. Ectopic expression of constitutively active <underline>mitogen -activated protein kinase kinase 1 (MKK1)</underline> resulted in activation of ERK1/2, and partially prevented CPX inhibition of LEC tube formation. The results suggest that CPX inhibits LEC tube formation at least in part through inhibiting VEGFR-3-mediated ERK signaling pathway.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Alitalo, K" uniqKey="Alitalo K">K Alitalo</name></author><author><name sortKey="Carmeliet, P" uniqKey="Carmeliet P">P Carmeliet</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ando, T" uniqKey="Ando T">T Ando</name></author><author><name sortKey="Jordan, P" uniqKey="Jordan P">P Jordan</name></author><author><name sortKey="Joh, T" uniqKey="Joh T">T Joh</name></author><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y Wang</name></author><author><name sortKey="Jennings, Mh" uniqKey="Jennings M">MH Jennings</name></author><author><name sortKey="Houghton, J" uniqKey="Houghton J">J Houghton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Clement, Pm" uniqKey="Clement P">PM 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sortKey="Zhou, H" uniqKey="Zhou H">H Zhou</name></author><author><name sortKey="Shen, T" uniqKey="Shen T">T Shen</name></author><author><name sortKey="Luo, Y" uniqKey="Luo Y">Y Luo</name></author><author><name sortKey="Liu, L" uniqKey="Liu L">L Liu</name></author><author><name sortKey="Chen, W" uniqKey="Chen W">W Chen</name></author><author><name sortKey="Xu, B" uniqKey="Xu B">B Xu</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>France</li><li>République populaire de Chine</li><li>États-Unis</li></country><region><li>Midi-Pyrénées</li><li>Occitanie (région administrative)</li></region><settlement><li>Toulouse</li></settlement></list><tree><country name="États-Unis"><noRegion><name sortKey="Luo, Yan" sort="Luo, Yan" uniqKey="Luo Y" first="Yan" last="Luo">Yan Luo</name></noRegion><name sortKey="Alexander, J Steven" sort="Alexander, J Steven" uniqKey="Alexander J" first="J. Steven" last="Alexander">J. Steven Alexander</name><name sortKey="Chen, Wenxing" sort="Chen, Wenxing" uniqKey="Chen W" first="Wenxing" last="Chen">Wenxing Chen</name><name sortKey="Han, Xiuzhen" sort="Han, Xiuzhen" uniqKey="Han X" first="Xiuzhen" last="Han">Xiuzhen Han</name><name sortKey="Huang, Shile" sort="Huang, Shile" uniqKey="Huang S" first="Shile" last="Huang">Shile Huang</name><name sortKey="Huang, Shile" sort="Huang, Shile" uniqKey="Huang S" first="Shile" last="Huang">Shile Huang</name><name sortKey="Liu, Lei" sort="Liu, Lei" uniqKey="Liu L" first="Lei" last="Liu">Lei Liu</name><name sortKey="Scott, Rona S" sort="Scott, Rona S" uniqKey="Scott R" first="Rona S." last="Scott">Rona S. Scott</name><name sortKey="Shen, Tao" sort="Shen, Tao" uniqKey="Shen T" first="Tao" last="Shen">Tao Shen</name><name sortKey="Xu, Baoshan" sort="Xu, Baoshan" uniqKey="Xu B" first="Baoshan" last="Xu">Baoshan Xu</name><name sortKey="Zhang, Fangfang" sort="Zhang, Fangfang" uniqKey="Zhang F" first="Fangfang" last="Zhang">Fangfang Zhang</name><name sortKey="Zhou, Hongyu" sort="Zhou, Hongyu" uniqKey="Zhou H" first="Hongyu" last="Zhou">Hongyu Zhou</name></country><country name="République populaire de Chine"><noRegion><name sortKey="Luo, Yan" sort="Luo, Yan" uniqKey="Luo Y" first="Yan" last="Luo">Yan Luo</name></noRegion></country><country name="France"><region name="Occitanie (région administrative)"><name sortKey="Alam, Antoine" sort="Alam, Antoine" uniqKey="Alam A" first="Antoine" last="Alam">Antoine Alam</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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