The advancements in targeted therapeutic strategies for breast cancer via intervention of natural molecules: An insight into cellular and molecular mechanisms.

Breast cancer (BC) is the most common cancer and a major cause of cancer-related deaths in women worldwide. Its significant molecular heterogeneity leads to different response rates, leaving standard therapy approaches comparatively ineffective. Recent evidence highlights the promise of natural compound-based therapies in modulating oncogenic signaling, regulating epigenetic mechanisms, and reshaping the tumor microenvironment. This review systematically explores the anticancer potential of bioactive phytochemicals, including curcumin, resveratrol, thymoquinone, and berberine, in BC. These agents exhibit pleiotropic mechanisms such as promoting apoptosis (e.g., via p53 activation), suppressing angiogenesis (e.g., through VEGF downregulation), and reversing chemoresistance (e.g., by inhibiting the PI3K/AKT/mTOR axis). The role of epigenetic regulation is explored, focusing on DNA methylation, histone modifications, and non-coding RNAs. Compounds like EGCG and ellagic acid have been shown to restore the expression of tumor suppressor genes. Special attention is given to different types of breast cancer, especially triple-negative breast cancer (TNBC), which currently has limited treatment options and poor outcomes. Laboratory studies suggest that plant-based compounds can enhance the sensitivity of TNBC cells to standard chemotherapy, while also impacting immune and metabolic functions. Advances in nanotechnology, such as liposome-encapsulated curcumin, gold nanoparticles containing berberine, and nano-delivery systems for resveratrol, have improved the absorption and effectiveness of these substances. In conclusion, natural compounds represent a valuable source of novel therapeutics for breast cancer management, bridging molecular insights with translational potential.