Effect of naringin, a natural compound, on stem cell phenotype of breast cancer

Almost all of novel therapies focused to target signaling pathways related to cell growth and survival failed to provide patient survival. These kinds of therapeutic approaches shrink just the tumor bulk and eventually lead to recurrence of cancer. This clinical handicap could be explained by the discovery of cancer stem cell (CSC) which resistant to standard therapies including chemo- and radiotherapy in different cancer types. The residual tumors after conventional therapies are enriched for CSCs and possess epithelial-mesenchymal transition (EMT)-like properties that promote invasion, metastasis. Natural dietary compounds, especially polyphenols have gained increasing attention due to their role in cancer chemoprevention. Recently, various studies showed that many natural compounds may decrease therapy-resistant, slow cycling cancer stem cell proportion and suppress EMT-like features. In this study, we tested the effect of naringin, a polyphenolic compound derived from grapefruit on the stem cell phenotype of breast cancer. The results showed that naringin treatment lead to decrease the fraction of CSCs and suppress the expression of EMT markers. It was demonstrated that this flavonoid at the concentration that does not cause cell cytotoxicity may affect stem cell properties of breast carcinoma by decreasing number of cells having high ALDH1 activity and CD44+/CD24-phenotype. These data suggest for the first time that naringin could be used to target Breast CSCs and provide over-all survival if used with an agent that eradicates differentiated cells.