Abstract | BACKGROUND: METHODS: A panel of eight breast cancer cell lines, including five estrogen receptor (ER)-positive and three ER-negative cell lines, was used. These cells were treated with eribulin and/or the antiestrogen, 4-hydroxytamoxifen or fulvestrant. Their growth inhibitory activities and effects on cell cycle progression, apoptosis, and the CSC population were investigated. CSCs were detected using the CD44/CD24/ EpCAM, Aldefluor, and mammosphere assays. RESULTS: The 50% growth inhibitory concentrations of eribulin were 0.38-2.64 nM for the eight cell lines tested. Eribulin exhibited significant antitumor activity under estrogen-supplemented conditions in ER-positive breast cancer cells. The combined antitumor activity of eribulin with an antiestrogen was evaluated using the combination index. The combination index was 0.43-1.46 for ER-positive cell lines. The additive antitumor effect of eribulin with 4-OHT was only significant in MCF-7 cells. Eribulin induced the accumulation of G2/M and apoptosis, while antiestrogens induced the retardation of G1-S cell cycle and apoptosis, respectively. Estrogen markedly increased the proportion of CSCs, whereas antiestrogens inhibited increases in ER-positive cell lines. Moreover, eribulin decreased the proportion of CSCs in either ER-positive or ER-negative cell lines. The combined treatment of eribulin with an antiestrogen did not additively decrease the proportion of CSCs in ER-positive cell lines. DISCUSSION: The results of the present study demonstrated that eribulin had potent antitumor effects on estrogen-stimulated ER-positive breast cancer cells and the combined treatment of eribulin with an antiestrogen resulted in a weakly additive antitumor effect. We herein suggested for the first time that eribulin exhibited anti-CSC effects on either ER-positive or ER-negative breast cancer cells.
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Authors | Junichi Kurebayashi, Naoki Kanomata, Tetsumasa Yamashita, Toshiro Shimo, Takuya Moriya |
Journal | Breast cancer (Tokyo, Japan)
(Breast Cancer)
Vol. 23
Issue 3
Pg. 425-36
(May 2016)
ISSN: 1880-4233 [Electronic] Japan |
PMID | 25552385
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Estrogen Antagonists
- Furans
- Ketones
- Tamoxifen
- afimoxifene
- Fulvestrant
- Estradiol
- eribulin
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Topics |
- Antineoplastic Agents
(pharmacology)
- Antineoplastic Combined Chemotherapy Protocols
(pharmacology)
- Apoptosis
(drug effects)
- Breast Neoplasms
(drug therapy, pathology)
- Cell Cycle
(drug effects)
- Cell Line, Tumor
- Estradiol
(administration & dosage, analogs & derivatives)
- Estrogen Antagonists
(administration & dosage, pharmacology)
- Female
- Fulvestrant
- Furans
(administration & dosage, pharmacology)
- Humans
- Ketones
(administration & dosage, pharmacology)
- Neoplastic Stem Cells
(drug effects, pathology)
- Tamoxifen
(administration & dosage, analogs & derivatives)
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