Eckol suppresses maintenance of sternness and malignancies in glioma stem-like cells
- Authors
- Hyun, Kyung-Hwan; Yoon, Chang-Hwan; Kim, Rae-Kwon; Lim, Eun-Jung; An, Sungkwan; Park, Myung-Jin; Hyun, Jin-Won; Suh, Yongjoon; Kim, Min-Jung; Lee, Su-Jae
- Issue Date
- Jul-2011
- Publisher
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Keywords
- Eckol; Glioma stem-like cells; Self-renewal; Malignant phenotype; Resistance to anticancer treatments
- Citation
- TOXICOLOGY AND APPLIED PHARMACOLOGY, v.254, no.1, pp.32 - 40
- Indexed
- SCIE
SCOPUS
- Journal Title
- TOXICOLOGY AND APPLIED PHARMACOLOGY
- Volume
- 254
- Number
- 1
- Start Page
- 32
- End Page
- 40
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/28112
- DOI
- 10.1016/j.taap.2011.04.006
- ISSN
- 0041-008X
- 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 sternness 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 sternness 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. (C) 2011 Elsevier Inc. All rights reserved.
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