Emerging role of plant-based compounds as ferroptosis modulators in breast cancer

Ferroptosis is a specialized form of regulated cell death that is dependent on intracellular iron and is characterized by excessive lipid peroxidation, accumulation of lipid peroxides, and increased intracellular iron levels. This process is regulated through complex and tightly coordinated molecular mechanisms involving multiple signaling pathways and regulatory proteins, including key antioxidant defense components such as glutathione peroxide 4 (GPX4) and ferroptosis suppressor protein-1 (FSP-1). Increasing experimental evidences suggested that modulation of ferroptosis pathway might offer a potent target for breast cancer management, as ferroptosis dysregulation has been strongly associated with tumor invasion, progression, and drug resistance. Current cancer treatment strategies including surgery, chemotherapy, radiation therapy have detrimental effects on cancer patients. Therefore, it is highly needed to focus on safe and effective therapeutics like natural compounds for cancer therapy. These compounds have shown the significance of ferroptosis-mediated cell death, thereby providing drug candidate for developing ferroptosis-inducing agents. Current research studies suggested that numerous plant-based compounds have strong anticancer potential via ferroptosis induction in breast carcinoma. However, these results are dependent upon preclinical experimentation and lacking validation of long-term clinical research. Thus, this review is designed to provide a mechanistic overview of plant-derived natural compounds by targeting ferroptosis pathway specifically in breast cancer. This could help the researchers working in medicinal chemistry field and pharmacology to better understand the mechanism of action of these compounds against breast carcinoma and provide an alternative approach to treat breast cancer.