title: Mulberry leaf extract inhibits cancer cell stemness in neuroblastoma.
abstract: Emerging evidence proposes that most cancers originate from a rare subpopulation of cells, called cancer stem cells (CSCs), which possess characteristics including differentiation, self-renewal, and tumorigenicity. Currently, available therapeutic agents cannot effectively eliminate CSCs. Therefore, the development of a nontoxic, natural treatment that can either overcome chemoresistance or promote the elimination of CSCs is highly desirable. The current study examined whether mulberry leaf (ML) ethanolic extract can effectively eliminate neuroblastoma stem cell-like population. Our data demonstrated that 10-40 μg/ml of ML extract significantly enhanced differentiation by elongating neurites and reducing clonogenicity and sphere formation as shown by the decreased expression of stem cell markers and increased expression of differentiation markers. The knock-down of delta-like 1 homologue by siRNA enhanced the significant inhibitory effects of 40 μg/ml of ML extract on colony formation. Furthermore, phosphorylation of the extracellular signal-regulated kinase (ERK) was increased by 20 or 40 μg/ml of ML extract and the MEK/ERK inhibitors completely blocked differentiation induced by the extract. Taken together, these findings provide experimental evidence that ML may have chemopreventive effects on neuroblastoma cells by inhibiting CSCs characteristics as well as regulating CSCs pathways, which may provide a therapeutic option for controlling the growth of neuroblastoma cells.
authors.affiliation: Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, Korea.
authors.forename: Seolhyun
authors.initials: S
authors.lastname: Park
authors.forename: Jina
authors.initials: J
authors.lastname: Kim
authors.forename: Yuri
authors.initials: Y
authors.lastname: Kim
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D031625:Morus; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D016501:Neurites / Q000187:drug effects; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D034741:RNA, Small Interfering; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010936:Plant Extracts; D034741:RNA, Small Interfering; D048049:Extracellular Signal-Regulated MAP Kinases