Withaferin A in breast cancer therapy: multi-targeted modulation of redox homeostasis, autophagy, and apoptosis

Withaferin A (WA), a steroidal lactone from Withania somnifera, exerts multi-targeted anti-breast-cancer activity by modulating redox homeostasis, autophagy, and apoptosis. WA elevates reactive oxygen species, perturbs mitochondrial function, and suppresses NF-κB/STAT3 signaling, thereby inhibiting proliferation, epithelial-to-mesenchymal transition, metastasis, and breast cancer stem cell self-renewal. This review synthesizes preclinical and emerging clinical evidence from PubMed/MEDLINE, Scopus, Web of Science, Google Scholar, and ClinicalTrials.gov (January 2000–October 2025). Despite promising multi-pathway activity, limited oral bioavailability, model heterogeneity, and scarce human data hinder translation. Advanced nanoformulations and rigorously designed clinical trials are essential to realize WA’s therapeutic potential.