Inhibition of Mitochondrial Respiration Prevents BRAF-Mutant Melanoma Brain Metastasis

In 2019, a study investigated the role of mitochondrial respiration in BRAF-mutant melanoma brain metastasis. The researchers found that inhibiting mitochondrial respiration could prevent this metastasis. They used a BRAFV600E-driven mouse model and found that the inhibition significantly reduced the number of brain metastases. The study also explored the potential of β-sitosterol, a plant-derived compound, as a therapeutic agent against these metastases. β-sitosterol effectively reduced melanoma cell growth in vitro and inhibited brain metastasis formation in vivo by interfering with mitochondrial respiration, specifically by inhibiting mitochondrial complex I. This led to increased oxidative stress that resulted in apoptosis in tumor cells. The study concluded that β-sitosterol, due to its favorable tolerability and capacity to inhibit mitochondrial respiration, represents a promising adjuvant to BRAF inhibitor therapy in patients with, or at risk for, melanoma brain metastases.