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Novel anticancer activity of phloroglucinol against breast cancer stem-like cells.

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.
AuthorsRae-Kwon Kim, Nizam Uddin, Jin-Won Hyun, Changil Kim, Yongjoon Suh, Su-Jae Lee
JournalToxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 286 Issue 3 Pg. 143-50 (Aug 01 2015) ISSN: 1096-0333 [Electronic] United States
PMID25843036 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier Inc. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Phloroglucinol
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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