title: Scrophularia orientalis extract induces calcium signaling and apoptosis in neuroblastoma cells.
abstract: Effective neuroblastoma (NB) treatments are still limited despite treatment options available today. Therefore, this study attempted to identify novel plant extracts that have anticancer effects. Cytotoxicity and increased intracellular calcium levels were determined using the Sulforhodamine B (SRB) assay and Fluo4-AM (acetoxymethyl) staining and fluorescence microscopy in NB cells in order to screen a library of plant extracts. The current study examined the anticancer effects of a dichloromethane extract from Scrophularia orientalis L. (Scrophulariaceae), a plant that has been used in Traditional Chinese Medicine. This extract contained highly potent agents that significantly reduced cell survival and increased calcium levels in NB cells. Further analysis revealed that cell death induced by this extract was associated with intracellular calcium release, opening of the MPTP, caspase 3- and PARP-cleavage suggesting that this extract induced aberrant calcium signaling that resulted in apoptosis via the mitochondrial pathway. Therefore, agents from Scrophularia orientalis may have the potential to lead to new chemo-therapeutic anticancer drugs. Furthermore, targeting intracellular calcium signaling may be a novel strategy to develop more effective treatments for NB.
authors: Daniel K. Inouye College of Pharmacy, University of Hawaii at Hilo, Hilo, HI, USA.
authors: Ingo
authors: I
authors: Lange
authors: Daniel K. Inouye College of Pharmacy, University of Hawaii at Hilo, Hilo, HI, USA.
authors: Julia
authors: J
authors: Moschny
authors: Institute of Botany, National Academy of Sciences, Yerevan, Armenia.
authors: Kamilla
authors: K
authors: Tamanyan
authors: National Herbarium of Georgia, Institute of Botany, Ilia State University, Tbilisi, Georgia.
authors: Manana
authors: M
authors: Khutsishvili
authors: The New York Botanical Garden, Bronx, NY, USA.
authors: Daniel
authors: D
authors: Atha
authors: School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, P.R. China.
authors: Robert P
authors: RP
authors: Borris
authors: Daniel K. Inouye College of Pharmacy, University of Hawaii at Hilo, Hilo, HI, USA.
authors: Dana-Lynn
authors: DL
authors: Koomoa
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D020013:Calcium Signaling / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism; D009447:Neuroblastoma / Q000188:drug therapy / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D032266:Scrophularia / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts