Sodium butyrate induces apoptosis in MSN neuroblastoma cells in a calcium independent pathway
1Department of Cell Biology & Anatomy, New York Medical College, Valhalla, New York 10595, USA.
Abstract:
Sodium butyrate (NaBt), a histone deacetylase inhibitor, can cause apoptosis in a number of cancer cells. However, the mechanism of this action is poorly understood. Increased intracellular [Ca(2+)] level has been suggested as a likely mechanism, but there is little corroborating data. In this report we provide evidence that NaBt-treated MSN neuroblastoma cells undergo massive apoptosis in the presence of serum and regardless of external or internal [Ca(2+)] levels. Presented data suggest that apoptotic effect of NaBt is both time- and dose-dependent (LD50 1 mM); and that, presence of serum or cAMP, a second messenger molecule that modulates the apoptotic program in a wide variety of cells could not circumvent the apoptotic effect of NaBt. Our findings suggest that NaBt-induced apoptosis in MSN neuroblastoma cells occurs via a pathway that is independent of Ca(2+) flux, intracellular [Ca(2+)] or cAMP levels. Further, we also present data that exclude a role for PKC or histones acetylation.
Insights
Sodium butyrate (NaBt) induces apoptosis in neuroblastoma cells. This cell death pathway is independent of calcium levels, serum, or cAMP signaling.
Area of Science:
- Neuroscience
- Molecular Biology
- Cancer Research
Background:
- Sodium butyrate (NaBt) is a histone deacetylase inhibitor with known apoptotic effects on cancer cells.
- The precise mechanism underlying NaBt-induced apoptosis remains poorly understood.
- Elevated intracellular calcium ([Ca(2+)]) has been hypothesized as a key mediator, but supporting evidence is limited.
Purpose of the Study:
- To investigate the mechanism of sodium butyrate (NaBt)-induced apoptosis in MSN neuroblastoma cells.
- To determine the role of intracellular calcium levels, serum, and cAMP in NaBt-mediated apoptosis.
- To elucidate the signaling pathways involved in NaBt-induced cell death.
Main Methods:
- Treatment of MSN neuroblastoma cells with varying concentrations of sodium butyrate (NaBt).
- Assessment of apoptosis induction in the presence and absence of serum.
- Monitoring of intracellular and extracellular calcium ([Ca(2+)]) levels.
- Evaluation of the impact of cAMP modulation on NaBt-induced apoptosis.
- Analysis of the involvement of protein kinase C (PKC) and histone acetylation.
Main Results:
- NaBt induced massive apoptosis in MSN neuroblastoma cells, irrespective of external or internal calcium levels.
- The apoptotic effect of NaBt was time- and dose-dependent, with an LD50 of 1 mM.
- Serum and cAMP did not prevent the apoptotic effect of NaBt.
- Data excluded a significant role for Ca(2+) flux, intracellular [Ca(2+)], cAMP levels, PKC, or histone acetylation in NaBt-induced apoptosis.
Conclusions:
- NaBt-induced apoptosis in MSN neuroblastoma cells occurs through a mechanism independent of calcium signaling, serum, or cAMP.
- This study identifies a novel apoptotic pathway for NaBt in neuroblastoma cells.
- Further research is warranted to fully characterize the molecular players in this calcium- and cAMP-independent apoptotic pathway.
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