title: 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.
authors.affiliation: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Rae-Kwon
authors.initials: RK
authors.lastname: Kim
authors.affiliation: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Nizam
authors.initials: N
authors.lastname: Uddin
authors.affiliation: College of Medicine and Applied Radiological Science Research Institute, Jeju National University, Jeju-si 690-756, Republic of Korea.
authors.forename: Jin-Won
authors.initials: JW
authors.lastname: Hyun
authors.affiliation: Department of Biotechnology, Konkuk University, Chungju 380-701, Republic of Korea.
authors.forename: Changil
authors.initials: C
authors.lastname: Kim
authors.affiliation: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea. Electronic address: hiswork@hanmail.net.
authors.forename: Yongjoon
authors.initials: Y
authors.lastname: Suh
authors.affiliation: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791, Republic of Korea. Electronic address: sj0420@hanyang.ac.kr.
authors.forename: Su-Jae
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D010696:Phloroglucinol / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D010696:Phloroglucinol
keywords: Anticancer activity; Breast cancer stem-like cells; KRAS; Phloroglucinol; Relapse; Resistance to anticancer treatment