4.6 Article

Scrophularia orientalis extract induces calcium signaling and apoptosis in neuroblastoma cells

Journal

INTERNATIONAL JOURNAL OF ONCOLOGY
Volume 48, Issue 4, Pages 1608-1616

Publisher

SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2016.3373

Keywords

channels; transporters; endoplasmic reticulum; mitochondria

Categories

Funding

  1. Alex's Lemonade Stand Foundation Young Investigator Award [439744]
  2. NIH grants from National Cancer Institute Mentored Research Scientist Development Award (K01) [CA154758]
  3. National Institutes of General Medical Sciences [P20GM 103466]

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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.

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