Mitochondria-Targeted Honokiol Confers a Striking Inhibitory Effect on Lung Cancer via Inhibiting Complex I Activity
Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2018 |
|---|---|
| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:3 |
|---|---|
| Enthalten in: |
iScience - 3(2018) vom: 25. Mai, Seite 192-207 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Pan, Jing [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Immunology |
|---|
| Anmerkungen: |
Date Revised 31.03.2024 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.1016/j.isci.2018.04.013 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM290605873 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM290605873 | ||
| 003 | DE-627 | ||
| 005 | 20240331232039.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2018 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.isci.2018.04.013 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1358.xml |
| 035 | |a (DE-627)NLM290605873 | ||
| 035 | |a (NLM)30428319 | ||
| 035 | |a (PII)S2589-0042(18)30045-2 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Pan, Jing |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Mitochondria-Targeted Honokiol Confers a Striking Inhibitory Effect on Lung Cancer via Inhibiting Complex I Activity |
| 264 | 1 | |c 2018 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 31.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Immunology | |
| 650 | 4 | |a Medicinal and Aromatic Plants | |
| 650 | 4 | |a Natural Product Chemistry | |
| 700 | 1 | |a Lee, Yongik |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Gang |e verfasserin |4 aut | |
| 700 | 1 | |a Zielonka, Jacek |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Bajzikova, Martina |e verfasserin |4 aut | |
| 700 | 1 | |a Xiong, Donghai |e verfasserin |4 aut | |
| 700 | 1 | |a Tsaih, Shirng-Wern |e verfasserin |4 aut | |
| 700 | 1 | |a Hardy, Micael |e verfasserin |4 aut | |
| 700 | 1 | |a Flister, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Olsen, Christopher M |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yian |e verfasserin |4 aut | |
| 700 | 1 | |a Vang, Ole |e verfasserin |4 aut | |
| 700 | 1 | |a Neuzil, Jiri |e verfasserin |4 aut | |
| 700 | 1 | |a Myers, Charles R |e verfasserin |4 aut | |
| 700 | 1 | |a Kalyanaraman, Balaraman |e verfasserin |4 aut | |
| 700 | 1 | |a You, Ming |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t iScience |d 2018 |g 3(2018) vom: 25. Mai, Seite 192-207 |w (DE-627)NLM285332627 |x 2589-0042 |7 nnns |
| 773 | 1 | 8 | |g volume:3 |g year:2018 |g day:25 |g month:05 |g pages:192-207 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.isci.2018.04.013 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 3 |j 2018 |b 25 |c 05 |h 192-207 | ||