Abstract |
Poor prognosis of breast cancer patients is closely associated with metastasis and relapse. There is substantial evidence supporting that cancer stem-like cells (CSCs) are primarily responsible for relapse in breast cancer after anticancer treatment. However, there is a lack of suitable drugs that target breast cancer stem-like cells (BCSCs). Here, we report that phloroglucinol (PG), a natural phlorotannin component of brown algae, suppresses sphere formation, anchorage-independent colony formation and in vivo tumorigenicity. In line with these observations, treatment with PG also decreased CD44(+) cancer cell population as well as expression of CSC regulators such as Sox2, CD44, Oct4, Notch2 and β- catenin. Also, treatment with PG sensitized breast cancer cells to anticancer drugs such as cisplatin, etoposide, and taxol as well as to ionizing radiation. Importantly, PG inhibited KRAS and its downstream PI3K/AKT and RAF-1/ERK signaling pathways that regulate the maintenance of CSCs. Taken together, our findings implicate PG as a good candidate to target BCSCs and to prevent the disease relapse.
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Authors | Rae-Kwon Kim, Nizam Uddin, Jin-Won Hyun, Changil Kim, Yongjoon Suh, Su-Jae Lee |
Journal | Toxicology and applied pharmacology
(Toxicol Appl Pharmacol)
Vol. 286
Issue 3
Pg. 143-50
(Aug 01 2015)
ISSN: 1096-0333 [Electronic] United States |
PMID | 25843036
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier Inc. All rights reserved. |
Chemical References |
- Antineoplastic Agents
- Phloroglucinol
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Topics |
- Animals
- Antineoplastic Agents
(chemistry, pharmacology, therapeutic use)
- Breast Neoplasms
(drug therapy, pathology)
- Cell Death
(drug effects, physiology)
- Female
- Humans
- MCF-7 Cells
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Neoplastic Stem Cells
(drug effects, pathology)
- Phloroglucinol
(chemistry, pharmacology, therapeutic use)
- Xenograft Model Antitumor Assays
(methods)
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