dc.contributor.author | Pan, Jing | |
dc.contributor.author | Lee, Yongik | |
dc.contributor.author | Cheng, Gang | |
dc.contributor.author | Zielonka, Jacek | |
dc.contributor.author | Zhang, Qi | |
dc.contributor.author | Bajzikova, Martina | |
dc.contributor.author | Xiong, Donghai | |
dc.contributor.author | Tsaih, Shirng-Wern | |
dc.contributor.author | Hardy, Micael | |
dc.contributor.author | Flister, Michael | |
dc.contributor.author | Olsen, Christopher M | |
dc.contributor.author | Wang, Yian | |
dc.contributor.author | Vang, Ole | |
dc.contributor.author | Neuzil, Jiri | |
dc.contributor.author | Myers, Charles R | |
dc.contributor.author | Kalyanaraman, Balaraman | |
dc.contributor.author | You, Ming | |
dc.date.accessioned | 2019-08-01T04:08:03Z | |
dc.date.available | 2019-08-01T04:08:03Z | |
dc.date.issued | 2018 | |
dc.identifier.issn | 2589-0042 | |
dc.identifier.doi | 10.1016/j.isci.2018.04.013 | |
dc.identifier.uri | http://hdl.handle.net/10072/384335 | |
dc.description.abstract | We 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.peerreviewed | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | Elsevier | |
dc.relation.ispartofpagefrom | 192 | |
dc.relation.ispartofpageto | 207 | |
dc.relation.ispartofjournal | iScience | |
dc.relation.ispartofvolume | 3 | |
dc.subject.fieldofresearch | Biomedical and clinical sciences | |
dc.subject.fieldofresearchcode | 32 | |
dc.title | Mitochondria-Targeted Honokiol Confers a Striking Inhibitory Effect on Lung Cancer via Inhibiting Complex I Activity | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dc.type.code | C - Journal Articles | |
dcterms.license | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.description.version | Version 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.hasfulltext | Full Text | |
gro.griffith.author | Neuzil, Jiri | |