Xiuli Li1, Na Zhou2, Jin Wang3, Zhijie Liu4, Xiaohui Wang5, Qin Zhang5, Qingyan Liu4, Lifeng Gao4, Rong Wang6. 1. Key Laboratory of Pharmacology, Chifeng University, Hongshan, Chifeng, Inner Mongolia 024000, China. 2. Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao 266061, China. 3. Affiliated People's Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 010020, China. 4. Medical College of Chifeng University, Hongshan, Chifeng, Inner Mongolia 024000, China. 5. Affiliated Hospital of Chifeng University, Hongshan, Chifeng, Inner Mongolia 024000, China. 6. Key Laboratory of Tropical Biological Resources of Ministry of Education, Hainan University, Haikou, Hainan 570228, China; Department of Pharmacy, College of Marine Science, Hainan University, Haikou, Hainan 570228, China. Electronic address: wang832820@126.com.
Abstract
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+/CD24-CSC 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.
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+/CD24-CSC 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 micetumor 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.