Kazinol-E is a specific inhibitor of ERK that suppresses the enrichment of a breast cancer stem-like cell population
- Authors
- Jung, Yu-Chae; Han, Seula; Hua, Li; Ahn, Yeon-Hwa; Cho, Hyewon; Lee, Cheol-Jung; Lee, Hani; Cho, Yong-Yeon; Ryu, Jae-Ha; Jeon, Raok; Kim, Woo-Young
- Issue Date
- Feb-2016
- Publisher
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Keywords
- Breast cancer stem cell; Extracellular signal-regulated kinase (ERK) pathway; Kazinol-E
- Citation
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.470, no.2, pp 294 - 299
- Pages
- 6
- Journal Title
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- Volume
- 470
- Number
- 2
- Start Page
- 294
- End Page
- 299
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/9943
- DOI
- 10.1016/j.bbrc.2016.01.066
- ISSN
- 0006-291X
1090-2104
- Abstract
- Growing evidence shows that cancer stem-like cells (CSLCs) contribute to breast cancer recurrence and to its resistance to conventional therapies. The extracellular signal-regulated kinase (ERIC) signaling pathway is a major determinant in the control of diverse cellular processes, including the maintenance of CSLCs. In this study, we found that Kazinol-E, an antioxidant flavan from Broussonetia kazinoki, decreased the CSLC population of a breast cancer cell line, MCF7. The CSLC population, characterized by CD44 high/CD24 low expression or by high Aldehyde dehydrogenase 1 activity, was decreased by a concentration of Kazinol-E that did not affect the growth of bulk-cultured MCF7 cells. Kazinol-E did not decrease EGF-induced ERIC phosphorylation in CSLCs, but did block the phosphorylation of an ERK substrate, p90RSK2, at Thr359/Ser363. We further demonstrated that EGF-induced ERK activity was blocked by Kazinol-E in a wild-type K-Ras-expressing non-small cell lung cancer cell line H226B. An in vitro kinase assay with purified ERK1 and p90RSK2 as its substrate demonstrated a direct inhibition of ERK activity by Kazinol E. Additionally, a the molecular docking study provided putative binding modes of Kazinol-E into the ATP binding pocket of ERK1 Collectively, these results suggest that Kazinol-E is a direct inhibitor of ERK1, and more studies are warranted to develop this reagent for therapeutic breast CSLC targeting. (C) 2016 Elsevier Inc. All rights reserved.
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