THE EFFECT OF SODIUM-BUTYRATE ON THE GROWTH-CHARACTERISTICS OF HUMAN CERVIX TUMOR-CELLS

Sodium butyrate has been shown to affect cell proliferation, and, at concentrations above approximately 0.5 mM, to cause cell death in some tumour cell lines. When combined with cytotoxic drugs increase in chemosensitivity has been observed. We are presently carrying out a study of the combined effects of sodium butyrate and cytotoxic drugs on cultured cervix tumour cells. To provide a baseline for this study we have carried out a systematic investigation of the effects of sodium butyrate alone on the growth characteristics of cervix tumour cells cultured as multicell spheroids. This has shown that concentrations of n-butyrate of 0.005 mM to 0.50 mM decrease cell proliferation without inducing cell death, the effect increasing with increasing concentration. Butyrate concentrations > 0.50 mM cause cell death after a period of 5 to 15 days exposure, dependent on concentration. Concentrations of 0.010 mM and above cause fragmentation of, and increased cell shedding from, multicell spheroids, suggesting an effect on the cell surface. Concentrations of butyrate > 0.10 mM cause a considerable increase in the synthesis of cytokeratin, as shown by reaction with cytokeratin antibody. Correlated with this is a marked increase in cell size, concentrations of butyrate of 2.0 or 3.0 mM leading to an approximate doubling of cell diameter, followed by cell disintegration. The effects of butyrate < 0.25 mM are readily reversible. At concentrations > 0.25 mM the effects are reversible up to a limit of about 7 to 20 days depending on concentration, even when cytokeratin synthesis has been induced.