Bisphenol A disrupts mitochondrial homeostasis and promotes metabolic alterations in cervical cancer cells

Bisphenol A (BPA), a synthetic endocrine-disrupting chemical, has been implicated in several diseases, including cancer. However, its effects on mitochondrial function in cervical cancer (CC) remain poorly understood. We investigated the effects of BPA on mitochondrial structure and function in SiHa and CaSki CC cell lines. Confocal microscopy revealed that BPA (1 nM-1 µM) disrupted mitochondrial morphology, increased circularity (^*p < 0.05), and reduced branch length and content. BPA increased mitochondrial ROS (mtROS) and Ca²⁺ levels, decreased mitochondrial membrane potential (MMP) and mitochondrial mass, induced mtDNA depletion, and impaired oxidative respiration (OCR). Notably, BPA increased glucose uptake and lipid peroxidation while reducing the antioxidant (GSH and CAT) activity. A dose-dependent increase in mitochondrial lipid droplets (p < 0.001) was accompanied by opposite ATP trends: ATP levels increased in SiHa cells but decreased in CaSki cells. Western blot and qRT‒PCR revealed the cell type-specific regulation of PGC1α, TFAM, and DRP1. Molecular docking revealed strong binding of BPA to IDH2 (docking score - 7.38), MAOB (- 6.29), and HK2 (- 3.208), which was further validated by stable MD simulation. Thus, BPA may induce mitochondrial dysfunction, metabolic changes, and oxidative stress in CC cells in vitro, suggesting a potential role in cervical carcinogenesis that warrants further in vivo investigation.