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Article Publish Status: FREE
Abstract Title:

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

Abstract Source:

iScience. 2018 May 25 ;3:192-207. Epub 2018 Apr 22. PMID: 30428319

Abstract Author(s):

Jing Pan, Yongik Lee, Gang Cheng, Jacek Zielonka, Qi Zhang, Martina Bajzikova, Donghai Xiong, Shirng-Wern Tsaih, Micael Hardy, Michael Flister, Christopher M Olsen, Yian Wang, Ole Vang, Jiri Neuzil, Charles R Myers, Balaraman Kalyanaraman, Ming You

Article Affiliation:

Jing Pan

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 ?, 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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