Sodium butyrate induces p53 dependent and independent cell death in human brain tumor cells in primary culture <em>in vitro</em>

Abstract

The anticancer effect of sodium butyrate (Na-Bu) has been demonstrated in many model systems. In this study, effect of Na-Bu on the survival of human brain tumor cells in primary culture was analyzed. A total of 20 glioblastoma multiforme (GBM), 15 astrocytomas, 15 meningiomas and 32 neurofibromatosis type 2 (NF2) tumor tissues were minced and cultured in primary cultures and the status of Fas, Bax, Bcl-2, p21 and p53 proteins were analyzed by western blotting after 48 h of Na-Bu exposure. Na-Bu treatment caused 75-80% cell death and it also increased the level of Fas protein in GBMs, astrocytomas, and meningiomas with mutant p53 but not with wild type p53. All the NF2 tumors had wild type p53, they had a trace level of Fas protein and Na-Bu exposure caused little change in Fas level. These data suggest that Na-Bu caused p53-dependent and p53-independent cell death in the brain tumors with wild type and mutant p53, respectively. All the Na-Bu treated samples had increased levels of pro-apoptotic Bax and anti-oncogenic p21 proteins, and decreased level of oncogenic, antiapoptotic Bcl-2 protein. These data indicate that the Na-Bu exposure caused cell death in these brain tumors due to apoptosis. Na-Bu could be developed as a therapeutic agent in the management of human brain tumors regardless of the p53 mutation status.