Mitochondria-targeted magnolol inhibits OXPHOS, proliferation, and tumor growth via modulation of energetics and autophagy in melanoma cells. (2020)

• Record Type: Journal Article
• Authors: Cheng, Gang; Hardy, Micael; Zielonka, Jacek; Weh, Katherine; Zielonka, Monika; Boyle, Kathleen A.; Abu Eid, Mahmoud; McAllister, Donna; Bennett, Brian; Kresty, Laura A.; Dwinell, Michael B.; Kalyanaraman, Balaraman
• Is Part Of: Cancer treatment and research communications. Number 25(2020)
• Publication Date: 2020
• Subjects: Bioenergetic metabolism -- Mitophagy -- Melanoma -- Mitochondria-targeted agents -- Oxidative phosphorylation
• DOI: 10.1016/j.ctarc.2020.100210
• Languages: English
• ISSNs: 2468-2942

Abstract

Highlights: Mito-magnolol is nearly 100-fold more effective than magnolol. Mito-magnolol inhibits mitochondrial respiration and melanoma cell proliferation. Mito-magnolol induces reactive oxygen species, peroxiredoxin oxidation, and mitophagy. 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.