The Natural Compound Fucoidan From New Zealand Undaria Pinnatifida Synergizes With the ERBB Inhibitor Lapatinib Enhancing Melanoma Growth Inhibition

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aut.relation.journalOncotargeten_NZ
aut.researcherLu, Jun
dc.contributor.authorThakur, Ven_NZ
dc.contributor.authorLu, Jen_NZ
dc.contributor.authorRoscilli, Gen_NZ
dc.contributor.authorAurisicchio, Len_NZ
dc.contributor.authorCappelletti, Men_NZ
dc.contributor.authorPavoni, Een_NZ
dc.contributor.authorWhite, WLen_NZ
dc.contributor.authorBedogni, Ben_NZ
dc.date.accessioned2017-05-18T00:43:29Z
dc.date.available2017-05-18T00:43:29Z
dc.date.copyright2017-01-02en_NZ
dc.date.issued2017-01-02en_NZ
dc.description.abstractMelanoma remains one of the most aggressive and therapy-resistant cancers. Finding new treatments to improve patient outcomes is an ongoing effort. We previously demonstrated that melanoma relies on the activation of ERBB signaling, specifically of the ERBB3/ERBB2 cascade. Here we show that melanoma tumor growth is inhibited by 60% over controls when treated with lapatinib, a clinically approved inhibitor of ERBB2/EGFR. Importantly, tumor growth is further inhibited to 85% when the natural compound fucoidan from New Zealand U. pinnatifida is integrated into the treatment regimen. Fucoidan not only enhances tumor growth inhibition, it counteracts the morbidity associated with prolonged lapatinib treatment. Fucoidan doubles the cell killing capacity of lapatinib. These effects are associated with a further decrease in AKT and NFκB signaling, two key pathways involved in melanoma cell survival. Importantly, the enhancing cell killing effects of fucoidan can be recapitulated by inhibiting ERBB3 by either a specific shRNA or a novel, selective ERBB3 neutralizing antibody, reiterating the key roles played by this receptor in melanoma. We therefore propose the use of lapatinib or specific ERBB inhibitors, in combination with fucoidan as a new treatment of melanoma that potentiates the effects of the inhibitors while protecting from their potential side effects.en_NZ
dc.identifier.citationOncotarget, 8 (11), 17887.
dc.identifier.doi10.18632/oncotarget.14437en_NZ
dc.identifier.issn1949-2553en_NZ
dc.identifier.urihttps://hdl.handle.net/10292/10481
dc.languageengen_NZ
dc.publisherImpact Journals
dc.relation.urihttp://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5b%5d=14437
dc.rightsOncotarget applies the Creative Commons Attribution License (CC BY) to all works we publish (read the human-readable summary or the full license legal code). Under the CC BY, authors retain ownership of the copyright for their article, but authors allow anyone to download, reuse, reprint, modify, distribute, and/or copy articles in Oncotarget, so long as the original authors and source are cited.
dc.rights.accessrightsOpenAccessen_NZ
dc.subjectERBB3en_NZ
dc.subjectFucoidanen_NZ
dc.subjectLapatiniben_NZ
dc.subjectMelanomaen_NZ
dc.subjectNatural compoundsen_NZ
dc.titleThe Natural Compound Fucoidan From New Zealand Undaria Pinnatifida Synergizes With the ERBB Inhibitor Lapatinib Enhancing Melanoma Growth Inhibitionen_NZ
dc.typeJournal Article
pubs.elements-id217875
pubs.organisational-data/AUT
pubs.organisational-data/AUT/Health & Environmental Science
pubs.organisational-data/AUT/Health & Environmental Science/Interprofessional Health
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