Abstract
Breast cancer stem cells (BCSCs) represent a highly aggressive subpopulation responsible for tumor initiation, recurrence, metastasis, and therapeutic resistance. Mitochondria play a central role in maintaining BCSC stemness through enhanced oxidative phosphorylation (OXPHOS), redox adaptation, and metabolic plasticity. Dysregulated mitochondrial dynamics and elevated reactive oxygen species (ROS) levels tightly modulate survival pathways, contributing to stemness maintenance. Curcumin, a pleiotropic phytochemical, has emerged as a promising agent capable of disrupting the ROS–mitochondria axis and modulating oncogenic signaling. Evidence indicates that curcumin alters mitochondrial biogenesis, suppresses OXPHOS, induces ROS-mediated mitochondrial dysfunction, and downregulates multiple pathways associated with BCSC maintenance, including PI3K/Akt/mTOR, Wnt/β-catenin, Ras, and p53. Despite its extensive anticancer potential, curcumin’s limited bioavailability has restricted its translation into clinical settings. Novel nanoformulations and targeted delivery approaches may enhance its therapeutic efficacy. This review provides a comprehensive analysis of the multimodal mechanisms through which curcumin targets BCSCs, with an emphasis on mitochondrial remodeling and ROS-driven vulnerabilities, offering a framework for future therapeutic development.