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dc.contributor.authorPan, Jing
dc.contributor.authorLee, Yongik
dc.contributor.authorCheng, Gang
dc.contributor.authorZielonka, Jacek
dc.contributor.authorZhang, Qi
dc.contributor.authorBajzikova, Martina
dc.contributor.authorXiong, Donghai
dc.contributor.authorTsaih, Shirng-Wern
dc.contributor.authorHardy, Micael
dc.contributor.authorFlister, Michael
dc.contributor.authorOlsen, Christopher M
dc.contributor.authorWang, Yian
dc.contributor.authorVang, Ole
dc.contributor.authorNeuzil, Jiri
dc.contributor.authorMyers, Charles R
dc.contributor.authorKalyanaraman, Balaraman
dc.contributor.authorYou, Ming
dc.date.accessioned2019-08-01T04:08:03Z
dc.date.available2019-08-01T04:08:03Z
dc.date.issued2018
dc.identifier.issn2589-0042
dc.identifier.doi10.1016/j.isci.2018.04.013
dc.identifier.urihttp://hdl.handle.net/10072/384335
dc.description.abstractWe synthesized a mitochondria-targeted honokiol (Mito-HNK) that facilitates its mitochondrial accumulation; this dramatically increases its potency and efficacy against highly metastatic lung cancer lines in vitro, and in orthotopic lung tumor xenografts and brain metastases in vivo. Mito-HNK is >100-fold more potent than HNK in inhibiting cell proliferation, inhibiting mitochondrial complex ǀ, stimulating reactive oxygen species generation, oxidizing mitochondrial peroxiredoxin-3, and suppressing the phosphorylation of mitoSTAT3. Within lung cancer brain metastases in mice, Mito-HNK induced the mediators of cell death and decreased the pathways that support invasion and proliferation. In contrast, in the non-malignant stroma, Mito-HNK suppressed pathways that support metastatic lesions, including those involved in inflammation and angiogenesis. Mito-HNK showed no toxicity and targets the metabolic vulnerabilities of primary and metastatic lung cancers. Its pronounced anti-invasive and anti-metastatic effects in the brain are particularly intriguing given the paucity of treatment options for such patients either alone or in combination with standard chemotherapeutics.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherElsevier
dc.relation.ispartofpagefrom192
dc.relation.ispartofpageto207
dc.relation.ispartofjournaliScience
dc.relation.ispartofvolume3
dc.subject.fieldofresearchBiomedical and clinical sciences
dc.subject.fieldofresearchcode32
dc.titleMitochondria-Targeted Honokiol Confers a Striking Inhibitory Effect on Lung Cancer via Inhibiting Complex I Activity
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2018 The Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International (CC BY-NC-ND 4.0) License, which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorNeuzil, Jiri


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