Quercetin suppresses breast cancer stem cells (CD44/CD24) by inhibiting the PI3K/Akt/mTOR-signaling pathway.

AIMS

Cancer stem cells (CSCs) are considered the prime source of cancer recurrence, metastasis, and progression and represent important targets for developing novel anticancer agents and therapeutic strategies. The aim of this study was to investigate the effect of treating breast CSCs with the anticancer flavonoid, quercetin.

MAIN METHODS

We examined changes in the cluster of differentiation CD44/CD24CSC population and behavior using the breast cancer cell line MCF-7.

KEY FINDINGS

Our results indicated that cell viability, clone formation, mammosphere generation, and nude mice tumor metastasis were inhibited in the CD44/CD24 population and that MCF-7 cells exhibited G1-phase arrest after quercetin treatment. Additionally, CyclinD1 and B cell lymphoma-2 expression were suppressed and Bcl-2-like protein-4 expression was enhanced after quercetin treatment. We also observed that estrogen receptor α and phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling were downregulated concurrently with the inhibition of CD44/CD24 viability and clone formation. Our findings suggested that quercetin treatment promoted weaker malignant activity associated with CSCs relative to that observed in normal cancer cells through its inhibition of the PI3K/Akt/mTOR-signaling pathway.

SIGNIFICANCE

These results indicated that CSCs are potential therapeutic targets for quercetin treatment of breast cancer.