PMID- 29355544 OWN - NLM STAT- MEDLINE DCOM- 20180226 LR - 20220408 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 196 DP - 2018 Mar 1 TI - Quercetin suppresses breast cancer stem cells (CD44(+)/CD24(-)) by inhibiting the PI3K/Akt/mTOR-signaling pathway. PG - 56-62 LID - S0024-3205(18)30020-1 [pii] LID - 10.1016/j.lfs.2018.01.014 [doi] AB - 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 alpha 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. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Li, Xiuli AU - Li X AD - Key Laboratory of Pharmacology, Chifeng University, Hongshan, Chifeng, Inner Mongolia 024000, China. FAU - Zhou, Na AU - Zhou N AD - Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao 266061, China. FAU - Wang, Jin AU - Wang J AD - Affiliated People's Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 010020, China. FAU - Liu, Zhijie AU - Liu Z AD - Medical College of Chifeng University, Hongshan, Chifeng, Inner Mongolia 024000, China. FAU - Wang, Xiaohui AU - Wang X AD - Affiliated Hospital of Chifeng University, Hongshan, Chifeng, Inner Mongolia 024000, China. FAU - Zhang, Qin AU - Zhang Q AD - Affiliated Hospital of Chifeng University, Hongshan, Chifeng, Inner Mongolia 024000, China. FAU - Liu, Qingyan AU - Liu Q AD - Medical College of Chifeng University, Hongshan, Chifeng, Inner Mongolia 024000, China. FAU - Gao, Lifeng AU - Gao L AD - Medical College of Chifeng University, Hongshan, Chifeng, Inner Mongolia 024000, China. FAU - Wang, Rong AU - Wang R AD - 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. LA - eng PT - Journal Article DEP - 20180121 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Antioxidants) RN - 0 (CD24 Antigen) RN - 0 (CD44 protein, human) RN - 0 (Hyaluronan Receptors) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 9IKM0I5T1E (Quercetin) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (Oncogene Protein v-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - Antioxidants/*pharmacology MH - Apoptosis/drug effects MH - CD24 Antigen/*drug effects MH - Female MH - G1 Phase/drug effects MH - Humans MH - Hyaluronan Receptors/*drug effects MH - MCF-7 Cells MH - Mice, Nude MH - Oncogene Protein v-akt/*antagonists & inhibitors MH - *Phosphoinositide-3 Kinase Inhibitors MH - Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors MH - Quercetin/*pharmacology MH - Signal Transduction/*drug effects MH - TOR Serine-Threonine Kinases/*antagonists & inhibitors MH - Xenograft Model Antitumor Assays OTO - NOTNLM OT - Breast cancer OT - Cancer stem cells OT - Quercetin EDAT- 2018/01/23 06:00 MHDA- 2018/02/27 06:00 CRDT- 2018/01/23 06:00 PHST- 2017/11/21 00:00 [received] PHST- 2018/01/05 00:00 [revised] PHST- 2018/01/13 00:00 [accepted] PHST- 2018/01/23 06:00 [pubmed] PHST- 2018/02/27 06:00 [medline] PHST- 2018/01/23 06:00 [entrez] AID - S0024-3205(18)30020-1 [pii] AID - 10.1016/j.lfs.2018.01.014 [doi] PST - ppublish SO - Life Sci. 2018 Mar 1;196:56-62. doi: 10.1016/j.lfs.2018.01.014. Epub 2018 Jan 21.