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Mitochondria-Targeted Honokiol Confers a Striking Inhibitory Effect on Lung Cancer via Inhibiting Complex I Activity
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SYSNO ASEP 0500606 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Mitochondria-Targeted Honokiol Confers a Striking Inhibitory Effect on Lung Cancer via Inhibiting Complex I Activity Author(s) Pan, J. (US)
Lee, Y. (US)
Cheng, G. (US)
Zielonka, J. (US)
Zhang, Q. (US)
Bajziková, Martina (BTO-N) RID
Xiong, D. (US)
Tsaih, S.-W. (US)
Hardy, M. (US)
Flister, M. (US)
Olsen, Ch.M. (US)
Wang, Y. (US)
Vang, O. (US)
Neužil, Jiří (BTO-N) RID
Myers, Ch. R. (US)
Kalyanaraman, B. (US)
You, M. (US)Number of authors 17 Source Title iScience. - : Cell Press
Roč. 3, MAY 25 2018 (2018), s. 192-207Number of pages 16 s. Language eng - English Country US - United States Keywords ANTIOXIDANT MITOQ ; SERINE PHOSPHORYLATION ; LIPOPHILIC CATIONS ; CARCINOMA-CELLS Subject RIV EB - Genetics ; Molecular Biology OECD category Biochemistry and molecular biology Institutional support BTO-N - RVO:86652036 UT WOS 000449721600016 DOI 10.1016/j.isci.2018.04.013 Annotation 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 |, stimulating reactive oxygen species generation, oxidizing mitochondrial peroxiredoxin-3, and suppressing the phosphorylation of mitoSTAT3. Within lung cancer brain metastases in mice, MitoHNK 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. Workplace Institute of Biotechnology Contact Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Year of Publishing 2019
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