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  • Mitochondria-Targeted Honokiol Confers a Striking Inhibitory Effect on Lung Cancer via Inhibiting Complex I Activity

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    Author(s)
    Pan, Jing
    Lee, Yongik
    Cheng, Gang
    Zielonka, Jacek
    Zhang, Qi
    Bajzikova, Martina
    Xiong, Donghai
    Tsaih, Shirng-Wern
    Hardy, Micael
    Flister, Michael
    Olsen, Christopher M
    Wang, Yian
    Vang, Ole
    Neuzil, Jiri
    Myers, Charles R
    Kalyanaraman, Balaraman
    You, Ming
    Griffith University Author(s)
    Neuzil, Jiri
    Year published
    2018
    Metadata
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    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 ...
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    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.
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    Journal Title
    iScience
    Volume
    3
    DOI
    https://doi.org/10.1016/j.isci.2018.04.013
    Copyright Statement
    © 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.
    Subject
    Medical and Health Sciences
    Publication URI
    http://hdl.handle.net/10072/384335
    Collection
    • Journal articles

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