Mitochondria-targeted magnolol inhibits OXPHOS, proliferation, and tumor growth via modulation of energetics and autophagy in melanoma cells
Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved..
INTRODUCTION: Melanoma is an aggressive form of skin cancer for which there are no effective drugs for prolonged treatment. The existing kinase inhibitor antiglycolytic drugs (B-Raf serine/threonine kinase or BRAF inhibitors) are effective for a short time followed by a rapid onset of drug resistance.
PRESENTATION OF CASE: Here, we show that a mitochondria-targeted analog of magnolol, Mito-magnolol (Mito-MGN), inhibits oxidative phosphorylation (OXPHOS) and proliferation of melanoma cells more potently than untargeted magnolol. Mito-MGN also inhibited tumor growth in murine melanoma xenografts. Mito-MGN decreased mitochondrial membrane potential and modulated energetic and mitophagy signaling proteins.
DISCUSSION: Results indicate that Mito-MGN is significantly more potent than the FDA-approved OXPHOS inhibitor in inhibiting proliferation of melanoma cells.
CONCLUSION: These findings have implications in the treatment of melanomas with enhanced OXPHOS status due to metabolic reprogramming or drug resistance.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:25 |
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| Enthalten in: |
Cancer treatment and research communications - 25(2020) vom: 15., Seite 100210 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cheng, Gang [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 17.11.2021 Date Revised 17.11.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ctarc.2020.100210 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM31557982X |
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| 100 | 1 | |a Cheng, Gang |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Mitochondria-targeted magnolol inhibits OXPHOS, proliferation, and tumor growth via modulation of energetics and autophagy in melanoma cells |
| 264 | 1 | |c 2020 | |
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| 500 | |a Date Completed 17.11.2021 | ||
| 500 | |a Date Revised 17.11.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved. | ||
| 520 | |a INTRODUCTION: Melanoma is an aggressive form of skin cancer for which there are no effective drugs for prolonged treatment. The existing kinase inhibitor antiglycolytic drugs (B-Raf serine/threonine kinase or BRAF inhibitors) are effective for a short time followed by a rapid onset of drug resistance | ||
| 520 | |a PRESENTATION OF CASE: Here, we show that a mitochondria-targeted analog of magnolol, Mito-magnolol (Mito-MGN), inhibits oxidative phosphorylation (OXPHOS) and proliferation of melanoma cells more potently than untargeted magnolol. Mito-MGN also inhibited tumor growth in murine melanoma xenografts. Mito-MGN decreased mitochondrial membrane potential and modulated energetic and mitophagy signaling proteins | ||
| 520 | |a DISCUSSION: Results indicate that Mito-MGN is significantly more potent than the FDA-approved OXPHOS inhibitor in inhibiting proliferation of melanoma cells | ||
| 520 | |a CONCLUSION: These findings have implications in the treatment of melanomas with enhanced OXPHOS status due to metabolic reprogramming or drug resistance | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a Bioenergetic metabolism | |
| 650 | 4 | |a Melanoma | |
| 650 | 4 | |a Mitochondria-targeted agents | |
| 650 | 4 | |a Mitophagy | |
| 650 | 4 | |a Oxidative phosphorylation | |
| 650 | 7 | |a Biphenyl Compounds |2 NLM | |
| 650 | 7 | |a Lignans |2 NLM | |
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| 700 | 1 | |a Zielonka, Jacek |e verfasserin |4 aut | |
| 700 | 1 | |a Weh, Katherine |e verfasserin |4 aut | |
| 700 | 1 | |a Zielonka, Monika |e verfasserin |4 aut | |
| 700 | 1 | |a Boyle, Kathleen A |e verfasserin |4 aut | |
| 700 | 1 | |a Abu Eid, Mahmoud |e verfasserin |4 aut | |
| 700 | 1 | |a McAllister, Donna |e verfasserin |4 aut | |
| 700 | 1 | |a Bennett, Brian |e verfasserin |4 aut | |
| 700 | 1 | |a Kresty, Laura A |e verfasserin |4 aut | |
| 700 | 1 | |a Dwinell, Michael B |e verfasserin |4 aut | |
| 700 | 1 | |a Kalyanaraman, Balaraman |e verfasserin |4 aut | |
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