Exploring The Relationship Between Mitochondrial-linked Cell Death And Muscle Atrophy During Ovarian Cancer Progression

The mechanisms underlying muscle atrophy during ovarian cancer are not fully understood. This study investigated the role of mitochondrial hydrogen peroxide (mH2O2)-mediated apoptosis and necroptosis in muscle atrophy using an orthotopic epithelial ovarian cancer (EOC) model at 40 and 80 days of tumor progression. We also examined the effects of the mitochondrial-targeted antioxidant SkQ1 on mH2O2 levels, regulation of apoptosis and necroptosis, and atrophy. Contrary to existing literature, muscle atrophy preceded EOC-induced changes in mH2O2 emission, and SkQ1, despite lowering mH2O2, did not prevent atrophy. Apoptotic markers (mPT, caspase-3, -9 activity) were elevated early in EOC progression and remained high, while necroptosis markers (RIPK1, phosphorylated MLKL/total MLKL) decreased with cancer progression. EOC-induced changes in necroptosis were unaffected by SkQ1, whereas markers of apoptosis (caspase-3/-9 activities) were downregulated by SkQ1. This study lays a crucial foundation for future research into regulated cell death pathways as mechanisms of cancer-induced atrophy.