Nobiletin Inhibits CD36-Dependent Tumor Angiogenesis, Migration, Invasion, and Sphere Formation Through the Cd36/Stat3/Nf-Κb Signaling Axis

<p dir="ltr">Targeted cancer therapy with natural compounds is more effective than nontargeted therapy. Nobiletin is a flavonoid derived from citrus peel that has anticancer activity. Cluster of differentiation 36 (CD36) is a member of the class B scavenger receptor family that is in...

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محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Nipin Sp (11639983) (author)
مؤلفون آخرون: Dong Kang (186690) (author), Doh Kim (4166668) (author), Jong Park (118816) (author), Hyo Lee (3564848) (author), Hye Kim (3437315) (author), Pramod Darvin (153341) (author), Yeong-Min Park (171090) (author), Young Yang (2447650) (author)
منشور في: 2018
الموضوعات:
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author Nipin Sp (11639983)
author2 Dong Kang (186690)
Doh Kim (4166668)
Jong Park (118816)
Hyo Lee (3564848)
Hye Kim (3437315)
Pramod Darvin (153341)
Yeong-Min Park (171090)
Young Yang (2447650)
author2_role author
author
author
author
author
author
author
author
author_facet Nipin Sp (11639983)
Dong Kang (186690)
Doh Kim (4166668)
Jong Park (118816)
Hyo Lee (3564848)
Hye Kim (3437315)
Pramod Darvin (153341)
Yeong-Min Park (171090)
Young Yang (2447650)
author_role author
dc.creator.none.fl_str_mv Nipin Sp (11639983)
Dong Kang (186690)
Doh Kim (4166668)
Jong Park (118816)
Hyo Lee (3564848)
Hye Kim (3437315)
Pramod Darvin (153341)
Yeong-Min Park (171090)
Young Yang (2447650)
dc.date.none.fl_str_mv 2018-06-15T03:00:00Z
dc.identifier.none.fl_str_mv 10.3390/nu10060772
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Nobiletin_Inhibits_CD36-Dependent_Tumor_Angiogenesis_Migration_Invasion_and_Sphere_Formation_Through_the_Cd36_Stat3_Nf-_b_Signaling_Axis/25920115
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biomedical and clinical sciences
Oncology and carcinogenesis
nobiletin
Cluster of differentiation 36 (CD36)
signal transducer and activator of transcription 3 (STAT3)
nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)
angiogenesis
metastasis
tumorsphere
dc.title.none.fl_str_mv Nobiletin Inhibits CD36-Dependent Tumor Angiogenesis, Migration, Invasion, and Sphere Formation Through the Cd36/Stat3/Nf-Κb Signaling Axis
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <p dir="ltr">Targeted cancer therapy with natural compounds is more effective than nontargeted therapy. Nobiletin is a flavonoid derived from citrus peel that has anticancer activity. Cluster of differentiation 36 (CD36) is a member of the class B scavenger receptor family that is involved in importing fatty acids into cells. CD36 plays a role in tumor angiogenesis by binding to its ligand, thrombospondin-1 (TSP-1), and then interacting with transforming growth factor beta 1 (TGFβ1). CD36 is implicated in tumor metastasis through its roles in fatty acid metabolism. This study investigated the molecular mechanisms underlying nobiletin’s anticancer activity by characterizing its interactions with CD36 as the target molecule. We hypothesize that the anti-angiogenic activity of nobiletin involving its regulation of CD36 via signal transducer and activator of transcription 3 (STAT3) rather than through TSP-1. Gene analysis identified a Gamma interferon activation site (GAS) element in the CD36 gene promoter that acts as a STAT3 binding site, an interaction that was confirmed by ChIP assay. STAT3 interacts with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), suggesting that nobiletin also acts through the CD36/ (STAT3)/NF-κB signaling axis. Nobiletin inhibited CD36-dependent breast cancer cell migration and invasion as well as CD36-mediated tumor sphere formation. Taken together, these results suggest that nobiletin inhibits cancer stem cells in multiple ways.</p><h2>Other Information</h2><p dir="ltr">Published in: Nutrients<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/nu10060772" target="_blank">https://dx.doi.org/10.3390/nu10060772</a></p>
eu_rights_str_mv openAccess
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identifier_str_mv 10.3390/nu10060772
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/25920115
publishDate 2018
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spelling Nobiletin Inhibits CD36-Dependent Tumor Angiogenesis, Migration, Invasion, and Sphere Formation Through the Cd36/Stat3/Nf-Κb Signaling AxisNipin Sp (11639983)Dong Kang (186690)Doh Kim (4166668)Jong Park (118816)Hyo Lee (3564848)Hye Kim (3437315)Pramod Darvin (153341)Yeong-Min Park (171090)Young Yang (2447650)Biomedical and clinical sciencesOncology and carcinogenesisnobiletinCluster of differentiation 36 (CD36)signal transducer and activator of transcription 3 (STAT3)nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)angiogenesismetastasistumorsphere<p dir="ltr">Targeted cancer therapy with natural compounds is more effective than nontargeted therapy. Nobiletin is a flavonoid derived from citrus peel that has anticancer activity. Cluster of differentiation 36 (CD36) is a member of the class B scavenger receptor family that is involved in importing fatty acids into cells. CD36 plays a role in tumor angiogenesis by binding to its ligand, thrombospondin-1 (TSP-1), and then interacting with transforming growth factor beta 1 (TGFβ1). CD36 is implicated in tumor metastasis through its roles in fatty acid metabolism. This study investigated the molecular mechanisms underlying nobiletin’s anticancer activity by characterizing its interactions with CD36 as the target molecule. We hypothesize that the anti-angiogenic activity of nobiletin involving its regulation of CD36 via signal transducer and activator of transcription 3 (STAT3) rather than through TSP-1. Gene analysis identified a Gamma interferon activation site (GAS) element in the CD36 gene promoter that acts as a STAT3 binding site, an interaction that was confirmed by ChIP assay. STAT3 interacts with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), suggesting that nobiletin also acts through the CD36/ (STAT3)/NF-κB signaling axis. Nobiletin inhibited CD36-dependent breast cancer cell migration and invasion as well as CD36-mediated tumor sphere formation. Taken together, these results suggest that nobiletin inhibits cancer stem cells in multiple ways.</p><h2>Other Information</h2><p dir="ltr">Published in: Nutrients<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/nu10060772" target="_blank">https://dx.doi.org/10.3390/nu10060772</a></p>2018-06-15T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/nu10060772https://figshare.com/articles/journal_contribution/Nobiletin_Inhibits_CD36-Dependent_Tumor_Angiogenesis_Migration_Invasion_and_Sphere_Formation_Through_the_Cd36_Stat3_Nf-_b_Signaling_Axis/25920115CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/259201152018-06-15T03:00:00Z
spellingShingle Nobiletin Inhibits CD36-Dependent Tumor Angiogenesis, Migration, Invasion, and Sphere Formation Through the Cd36/Stat3/Nf-Κb Signaling Axis
Nipin Sp (11639983)
Biomedical and clinical sciences
Oncology and carcinogenesis
nobiletin
Cluster of differentiation 36 (CD36)
signal transducer and activator of transcription 3 (STAT3)
nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)
angiogenesis
metastasis
tumorsphere
status_str publishedVersion
title Nobiletin Inhibits CD36-Dependent Tumor Angiogenesis, Migration, Invasion, and Sphere Formation Through the Cd36/Stat3/Nf-Κb Signaling Axis
title_full Nobiletin Inhibits CD36-Dependent Tumor Angiogenesis, Migration, Invasion, and Sphere Formation Through the Cd36/Stat3/Nf-Κb Signaling Axis
title_fullStr Nobiletin Inhibits CD36-Dependent Tumor Angiogenesis, Migration, Invasion, and Sphere Formation Through the Cd36/Stat3/Nf-Κb Signaling Axis
title_full_unstemmed Nobiletin Inhibits CD36-Dependent Tumor Angiogenesis, Migration, Invasion, and Sphere Formation Through the Cd36/Stat3/Nf-Κb Signaling Axis
title_short Nobiletin Inhibits CD36-Dependent Tumor Angiogenesis, Migration, Invasion, and Sphere Formation Through the Cd36/Stat3/Nf-Κb Signaling Axis
title_sort Nobiletin Inhibits CD36-Dependent Tumor Angiogenesis, Migration, Invasion, and Sphere Formation Through the Cd36/Stat3/Nf-Κb Signaling Axis
topic Biomedical and clinical sciences
Oncology and carcinogenesis
nobiletin
Cluster of differentiation 36 (CD36)
signal transducer and activator of transcription 3 (STAT3)
nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)
angiogenesis
metastasis
tumorsphere