Scrophularia orientalis extract induces calcium signaling and apoptosis in neuroblastoma cells
Ingo Lange1, Julia Moschny1, Kamilla Tamanyan2
1Daniel K. Inouye College of Pharmacy, University of Hawaii at Hilo, Hilo, HI, USA.
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.
Insights
Novel plant extracts show promise for neuroblastoma (NB) treatment. Scrophularia orientalis extract effectively reduced NB cell survival and induced apoptosis via calcium signaling, suggesting potential for new anticancer drugs.
Area of Science:
- Pharmacology
- Cell Biology
- Natural Products Chemistry
Background:
- Neuroblastoma (NB) treatments remain limited, necessitating the search for novel therapeutic agents.
- Traditional Chinese Medicine offers a rich source of compounds with potential anticancer properties.
Purpose of the Study:
- To screen plant extracts for anticancer effects against neuroblastoma cells.
- To investigate the mechanism of action of a promising extract, focusing on intracellular calcium signaling.
Main Methods:
- Screening of plant extracts using Sulforhodamine B (SRB) assay for cytotoxicity.
- Assessment of intracellular calcium levels using Fluo4-AM staining and fluorescence microscopy.
- Analysis of apoptosis markers including mitochondrial pathway activation, caspase 3, and PARP cleavage.
Main Results:
- A dichloromethane extract from Scrophularia orientalis demonstrated significant cytotoxicity against NB cells.
- The extract markedly increased intracellular calcium levels in NB cells.
- Extract-induced cell death involved mitochondrial pathway activation, indicated by MPTP opening and caspase/PARP cleavage.
Conclusions:
- Scrophularia orientalis extract contains potent anticancer agents effective against neuroblastoma.
- Aberrant calcium signaling plays a critical role in the apoptotic mechanism induced by the extract.
- Targeting intracellular calcium signaling presents a novel therapeutic strategy for neuroblastoma treatment.
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