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. doi: 10.1016/j.ctarc.2020.100210. Epub 2020 Sep 17.


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.

Keywords: Bioenergetic metabolism; Melanoma; Mitochondria-targeted agents; Mitophagy; Oxidative phosphorylation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Autophagy / genetics*
  • Biphenyl Compounds / pharmacology
  • Biphenyl Compounds / therapeutic use*
  • Cell Line, Tumor
  • Cytoprotection
  • Humans
  • Lignans / pharmacology
  • Lignans / therapeutic use*
  • Melanoma / drug therapy*
  • Mice
  • Mice, Nude
  • Mitophagy / genetics*
  • Nitric Oxide Synthase / pharmacology
  • Nitric Oxide Synthase / therapeutic use*
  • Oxidative Phosphorylation / drug effects*


  • Biphenyl Compounds
  • Lignans
  • magnolol
  • Nitric Oxide Synthase