Faculty Collaboration Database

Mitochondria-Targeted Honokiol Confers a Striking Inhibitory Effect on Lung Cancer via Inhibiting Complex I Activity. iScience 2018 May 25;3:192-207

Date

11/15/2018

Pubmed ID

30428319

Pubmed Central ID

PMC6137433

DOI

10.1016/j.isci.2018.04.013

Scopus ID

2-s2.0-85063413951 (requires institutional sign-in at Scopus site)   42 Citations

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.

Author List

Pan J, Lee Y, Cheng G, Zielonka J, Zhang Q, Bajzikova M, Xiong D, Tsaih SW, Hardy M, Flister M, Olsen CM, Wang Y, Vang O, Neuzil J, Myers CR, Kalyanaraman B, You M

Authors

Gang Cheng PhD Assistant Professor in the Biophysics department at Medical College of Wisconsin
Micael Joel Hardy PhD Visiting Assistant Professor in the Biophysics department at Medical College of Wisconsin
Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of Wisconsin
Christopher M. Olsen PhD Associate Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Shirng-Wern Tsaih Research Scientist II in the Obstetrics and Gynecology department at Medical College of Wisconsin
Jacek M. Zielonka PhD Assistant Professor in the Biophysics department at Medical College of Wisconsin