Mitochondria-Targeted Honokiol Confers a Striking Inhibitory Effect on Lung Cancer via Inhibiting Complex I Activity
Status PubMed-not-MEDLINE Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články
Grantová podpora
R01 CA193343
NCI NIH HHS - United States
R01 CA208648
NCI NIH HHS - United States
PubMed
30428319
PubMed Central
PMC6137433
DOI
10.1016/j.isci.2018.04.013
PII: S2589-0042(18)30045-2
Knihovny.cz E-zdroje
- Klíčová slova
- Immunology, Medicinal and Aromatic Plants, Natural Product Chemistry,
- Publikační typ
- časopisecké články MeSH
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, 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.
Czech Academy of Sciences Prague Czech Republic
Czech Academy of Sciences Prague Czech Republic; Griffith University Queensland Australia
Department of Science and Environment Roskilde University Roskilde Denmark
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