Scrophularia orientalis extract induces calcium signaling and apoptosis in neuroblastoma cells

Lange,Ingo; Moschny,Julia; Tamanyan,Kamilla; Khutsishvili,Manana; Atha,Daniel; Borris,Robert P.; Koomoa,Dana-Lynn

doi:10.3892/ijo.2016.3373

Scrophularia orientalis extract induces calcium signaling and apoptosis in neuroblastoma cells

Authors:
- Ingo Lange
- Julia Moschny
- Kamilla Tamanyan
- Manana Khutsishvili
- Daniel Atha
- Robert P. Borris
- Dana-Lynn Koomoa
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Affiliations: Daniel K. Inouye College of Pharmacy, University of Hawaii at Hilo, Hilo, HI, USA, Institute of Botany, National Academy of Sciences, Yerevan, Armenia, National Herbarium of Georgia, Institute of Botany, Ilia State University, Tbilisi, Georgia, The New York Botanical Garden, Bronx, NY, USA, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, P.R. China
Published online on: February 3, 2016 https://doi.org/10.3892/ijo.2016.3373
Pages: 1608-1616

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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 chemotherapeutic anticancer drugs. Furthermore, targeting intracellular calcium signaling may be a novel strategy to develop more effective treatments for NB.

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