Premium
Mulberry leave extracts inhibit stem cell‐like human neuroblastoma cells through induction of differentiation, down‐regulation of delta‐like 1 homologue (DLK1), and inhibition of ERK pathway
Author(s) -
Park Seolhyun,
Kim Jina,
Kim Yuri
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.822.20
Subject(s) - neuroblastoma , stem cell , mapk/erk pathway , cancer research , cancer stem cell , biology , cell growth , homeobox protein nanog , cellular differentiation , microbiology and biotechnology , neural stem cell , neurite , cell , kinase , cell culture , embryonic stem cell , induced pluripotent stem cell , genetics , gene , in vitro
Neuroblastoma is a malignant tumor of the neural crest and the most prevalent pediatric solid tumor. Malignant neuroblastoma cells resemble stem cell/progenitor cells possessing differentiable and self‐renewal potential. Understanding the mechanism that regulates the characteristics of cancer stem cells is of greatest importance of discovery of chemotherapeutic treatment. Mulberry leaves are traditional medical plants and have been reported to have medical benefits, including antidiabetic, anti‐inflammatory, and anticancer effect. However, the effect of mulberry leaves on cancer stemness remains to be examined. In this present study, mulberry leaves extracts (MLE) inhibited cell growth in a timeand dose‐dependent manner. MLE enhanced neuronal differentiation by elongating neurites and significantly reduced clonogenicity and non‐adherent sphere formation. Western blot results demonstrated that MLE not only down‐regulated the expression of stem cell markers (notch‐1 and sox‐2), but also upregulated beta‐tubulin III, one of neuronal differentiation markers. Furthermore, MLE increased phosphorylation of ERK kinases, a mechanism that has been shown to facilitate neuronal differentiation and regulated the bona fide stem cell gene, delta‐like 1 homologue (DLK1), which indicated the involvement of MLE in stem cell regulation. Taken together, these findings provide experimental evidence that MLE may possess chemopreventive effect on neuroblastoma cells by inhibiting cancer stem cell characteristics as well as regulating cancer‐stem cell pathway, which enable us to discover more preventive strategies for this deadly child cancer, thereby improve patient survival. [This research was supported by Ewha Womans University Research Grant of 2010 (Project Number is 2010‐0256‐1‐2)]