title: Eckol suppresses maintenance of stemness and malignancies in glioma stem-like cells.
abstract: A subpopulation of cancer cells with stem cell properties is responsible for tumor maintenance and progression, and may contribute to resistance to anticancer treatments. Thus, compounds that target cancer stem-like cells could be usefully applied to destroy cancer. In this study, we investigated the effect of Eckol, a phlorotannin compound, on stemness and malignancies in glioma stem-like cells. To determine whether Eckol targets glioma stem-like cells, we examined whether Eckol treatment could change the expression levels of glioma stem-like cell markers and self-renewal-related proteins as well as the sphere forming ability, and the sensitivity to anticancer treatments. Alterations in the malignant properties of sphere-derived cells by Eckol were also investigated by soft-agar colony forming assay, by xenograft assay in nude mice, and by cell invasion assay. Treatment of sphere-forming glioma cells with Eckol effectively decreased the sphere formation as well as the CD133(+) cell population. Eckol treatment suppressed expression of the glioma stem-like cell markers and the self-renewal-related proteins without cell death. Moreover, treatment of glioma stem-like cells with Eckol significantly attenuated anchorage-independent growth on soft agar and tumor formation in xenograft mice. Importantly, Eckol treatment effectively reduced the resistance of glioma stem-like cells to ionizing radiation and temozolomide. Treatment of glioma stem-like cells with Eckol markedly blocked both phosphoinositide 3-kinase-Akt and Ras-Raf-1-Erk signaling pathways. These results indicate that the natural phlorotannin Eckol suppresses stemness and malignancies in glioma stem-like cells, and thereby makes glioma stem-like cells more sensitive to anticancer treatments, providing novel therapeutic strategies targeting specifically cancer stem-like cells.
authors.affiliation: Department of Chemistry, Research Institute for Natural Sciences, Hanyang University, Seoul, Republic of Korea.
authors.forename: Kyung-Hwan
authors.initials: KH
authors.lastname: Hyun
authors.forename: Chang-Hwan
authors.initials: CH
authors.lastname: Yoon
authors.forename: Rae-Kwon
authors.initials: RK
authors.lastname: Kim
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Lim
authors.forename: Sungkwan
authors.initials: S
authors.lastname: An
authors.forename: Myung-Jin
authors.initials: MJ
authors.lastname: Park
authors.forename: Jin-Won
authors.initials: JW
authors.lastname: Hyun
authors.forename: Yongjoon
authors.initials: Y
authors.lastname: Suh
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Kim
authors.forename: Su-Jae
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004147:Dioxins / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004147:Dioxins; C060311:eckol; D019869:Phosphatidylinositol 3-Kinases; D019908:Proto-Oncogene Proteins c-raf