Enhanced Apoptosis in Transformed Human Lung Fibroblasts after Exposure to Sodium Butyrate

Simian virus-transformed human cells, WI-38 VA13A, showed a dose-dependent induction of apoptosis and reduction in cell numbers after exposure to sodium butyrate. Apoptosis was confirmed by ApopTag staining, isolation of apoptotic envelopes, and immunofluorescent staining with an antibody specific for apoptotic envelopes. Examination of the cell cultures by phase contrast and fluorescent microscopy revealed the presence of enlarged cells that displayed a more flattened morphology and morphological changes in the nucleus of cells exposed to sodium butyrate. Cell proliferation assays showed control and sodium butyrate cultures were synthesizing DNA and excluded any cytotoxic effects of sodium butyrate. Flow cytometry results indicated an increase in the number of aneuploid cells following sodium butyrate treatment. There was a decrease in the percentage of cells in G2/M in the diploid populations, but an increase in the percentage of cells in G2/M in aneuploid populations. This human in vitro model system suggests a mode of action for the therapeutic effects of sodium butyrate, which have been observed in the topical treatment of neoplastic cells and reversal of symptoms in ulcerative colitis: namely, the induction of apoptosis.