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Mitochondria-targeted magnolol inhibits OXPHOS, proliferation, and tumor growth via modulation of energetics and autophagy in melanoma cells. Cancer Treat Res Commun 2020;25:100210

Date

09/29/2020

Pubmed ID

32987287

Pubmed Central ID

PMC7883397

DOI

10.1016/j.ctarc.2020.100210

Scopus ID

2-s2.0-85091576205 (requires institutional sign-in at Scopus site)   19 Citations

Abstract

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.

Author List

Cheng G, Hardy M, Zielonka J, Weh K, Zielonka M, Boyle KA, Abu Eid M, McAllister D, Bennett B, Kresty LA, Dwinell MB, Kalyanaraman B

Authors

Brian Bennett D.Phil. Professor and Chair in the Physics department at Marquette University
Gang Cheng PhD Assistant Professor in the Biophysics department at Medical College of Wisconsin
Michael B. Dwinell PhD Director, Professor in the Microbiology and Immunology 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
Jacek M. Zielonka PhD Assistant Professor in the Biophysics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Autophagy
Biphenyl Compounds
Cell Line, Tumor
Cytoprotection
Humans
Lignans
Melanoma
Mice
Mice, Nude
Nitric Oxide Synthase
Oxidative Phosphorylation