Eckol suppresses maintenance of stemness and malignancies in glioma stem-like cells

Journal Article · Fri Jul 01 00:00:00 EDT 2011 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2011.04.006· OSTI ID:21587779

Hyun, Kyung-Hwan; Yoon, Chang-Hwan; Kim, Rae-Kwon; Lim, Eun-Jung ^[1]; An, Sungkwan ^[2]; Park, Myung-Jin ^[3]; Hyun, Jin-Won ^[4]; Suh, Yongjoon ^[1]; Kim, Min-Jung ^[1]; Lee, Su-Jae ^[1]

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1. Department of Chemistry, Research Institute for Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of)
2. Functional Genoproteome Research Centre, Konkuk University, Seoul 143-701 (Korea, Republic of)
3. Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)
4. College of Medicine and Applied Radiological Science Research Institute, Jeju National University, Jeju-si 690-756 (Korea, Republic of)

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{sup +} 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.

• OSTI ID: 21587779
• Journal Information: Toxicology and Applied Pharmacology, Vol. 254, Issue 1; Other Information: DOI: 10.1016/j.taap.2011.04.006; PII: S0041-008X(11)00135-9; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AGAR
APOPTOSIS
GLIOMAS
IONIZING RADIATIONS
MICE
POPULATIONS
PROTEINS
RNA
SPHERES
STEM CELLS
ANIMAL CELLS
ANIMALS
CARBOHYDRATES
COLLOIDS
DISEASES
DISPERSIONS
MAMMALS
NEOPLASMS
NERVOUS SYSTEM DISEASES
NUCLEIC ACIDS
ORGANIC COMPOUNDS
POLYSACCHARIDES
RADIATIONS
RODENTS
SACCHARIDES
SOMATIC CELLS
VERTEBRATES