Kazinol-E is a specific inhibitor of ERK that suppresses the enrichment of a breast cancer stem-like cell population

Biochemical and Biophysical Research Communications
Yu-Chae JungWoo-Young Kim

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 (ERK) 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 ERK 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 p...Continue Reading

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Citations

Jan 31, 2017·Chemical & Pharmaceutical Bulletin·Heejoo ParkWoo-Young Kim
Mar 15, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Da Yeon LeeJae-Ha Ryu
Mar 4, 2021·International Journal of Nanomedicine·Li LvGuocheng Li

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