Targeting breast cancer stem cells with natural compounds: mechanisms and therapeutic prospects

Breast cancer is the most frequently diagnosed malignancy among women worldwide, affecting more than 2 million people annually. Despite significant advances in diagnosis and treatment, the mortality rate has increased in recent years. Patient mortality is primarily attributed to disease recurrence, metastasis, and resistance to therapy. It is known that cancer stem cells (CSCs) in cancer tissues, which can self-renew and generate heterogeneous cancer cell lineages, play an essential role in the initiation, progression, metastasis, and treatment resistance. Therefore, their ablation is a practical approach to the treatment of BC. Using natural compounds has been proposed as a promising and effective strategy to eliminate stem cells. Natural products include plant metabolites such as polyphenols, flavonoids, alkaloids, and isothiocyanates, which can directly or indirectly affect CSCs due to their distinct biological characteristics, including antioxidant, anti-inflammatory, and pro-apoptotic activities, as well as the regulation of cell signaling pathways. These compounds often suppress the growth of CSC cells by targeting cellular markers such as ALDH1, CD44, and CXCRs, and critical signaling pathways such as Notch, Wnt/β-catenin, and Hedgehog, which are involved in the self-renewal and proliferation of CSCs. Finally, developing and using natural compounds as complementary or alternative therapies is a promising step to improve BC treatment. This study investigates the latest knowledge of BCSCs, emphasizing their biomarkers, signaling pathways, and drug resistance mechanisms, and then highlights the importance and mechanism of action of plant compounds in destroying them.