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

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 Kalynaraman, Ming You

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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 ǀ, 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.
OriginalsprogEngelsk
TidsskriftiScience
Vol/bind3
Sider (fra-til)192-207
Antal sider16
DOI
StatusUdgivet - 22 apr. 2018

Emneord

  • Mitochondria
  • Complex I
  • Cancer
  • Honokiol

Citer dette

Pan, Jing ; Lee, Yongik ; Cheng, Gang ; Zielonka, Jacek ; Zhang, Qi ; Bajzikova, Martina ; Xiong, Donghai ; Tsaih, Shirng-Wern ; Hardy, Micael ; Flister, Michael ; Olsen, Christopher M. ; Wang, Yian ; Vang, Ole ; Neuzil, Jiri ; Myers, Charles R. ; Kalynaraman, Balaraman ; You, Ming. / Mitochondria-Targeted Honokiol Confers a Striking Inhibitory Effect on Lung Cancer via Inhibiting Complex I Activity. I: iScience. 2018 ; Bind 3. s. 192-207.
@article{2f8b82d4272c4bddb71a7da0d6ebd19f,
title = "Mitochondria-Targeted Honokiol Confers a Striking Inhibitory Effect on Lung Cancer via Inhibiting Complex I Activity",
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 ǀ, 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.",
keywords = "Mitochondria, Complex I, Cancer, Honokiol",
author = "Jing Pan and Yongik Lee and Gang Cheng and Jacek Zielonka and Qi Zhang and Martina Bajzikova and Donghai Xiong and Shirng-Wern Tsaih and Micael Hardy and Michael Flister and Olsen, {Christopher M.} and Yian Wang and Ole Vang and Jiri Neuzil and Myers, {Charles R.} and Balaraman Kalynaraman and Ming You",
year = "2018",
month = "4",
day = "22",
doi = "10.1016/j.isci.2018.04.013",
language = "English",
volume = "3",
pages = "192--207",
journal = "iScience",

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Pan, J, Lee, Y, Cheng, G, Zielonka, J, Zhang, Q, Bajzikova, M, Xiong, D, Tsaih, S-W, Hardy, M, Flister, M, Olsen, CM, Wang, Y, Vang, O, Neuzil, J, Myers, CR, Kalynaraman, B & You, M 2018, 'Mitochondria-Targeted Honokiol Confers a Striking Inhibitory Effect on Lung Cancer via Inhibiting Complex I Activity' iScience, bind 3, s. 192-207. https://doi.org/10.1016/j.isci.2018.04.013

Mitochondria-Targeted Honokiol Confers a Striking Inhibitory Effect on Lung Cancer via Inhibiting Complex I Activity. / Pan, Jing; Lee, Yongik; Cheng, Gang; Zielonka, Jacek; Zhang, Qi; Bajzikova, Martina; Xiong, Donghai; Tsaih, Shirng-Wern; Hardy, Micael; Flister, Michael; Olsen, Christopher M.; Wang, Yian; Vang, Ole; Neuzil, Jiri; Myers, Charles R.; Kalynaraman, Balaraman; You, Ming.

I: iScience, Bind 3, 22.04.2018, s. 192-207.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Mitochondria-Targeted Honokiol Confers a Striking Inhibitory Effect on Lung Cancer via Inhibiting Complex I Activity

AU - Pan, Jing

AU - Lee, Yongik

AU - Cheng, Gang

AU - Zielonka, Jacek

AU - Zhang, Qi

AU - Bajzikova, Martina

AU - Xiong, Donghai

AU - Tsaih, Shirng-Wern

AU - Hardy, Micael

AU - Flister, Michael

AU - Olsen, Christopher M.

AU - Wang, Yian

AU - Vang, Ole

AU - Neuzil, Jiri

AU - Myers, Charles R.

AU - Kalynaraman, Balaraman

AU - You, Ming

PY - 2018/4/22

Y1 - 2018/4/22

N2 - 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 ǀ, 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.

AB - 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 ǀ, 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.

KW - Mitochondria

KW - Complex I

KW - Cancer

KW - Honokiol

U2 - 10.1016/j.isci.2018.04.013

DO - 10.1016/j.isci.2018.04.013

M3 - Journal article

VL - 3

SP - 192

EP - 207

JO - iScience

JF - iScience

ER -