Sodium Butyrate Induces Apoptosis in MSN Neuroblastoma Cells in a Calcium Independent Pathway

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 [Ca²⁺] 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 [Ca²⁺] 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 Ca²⁺flux, intracellular [Ca²⁺] or cAMP levels. Further, we also present data that exclude a role for PKC or histones acetylation.