Butyrate effects on growth, morphology, and fibronectin production in PC-3 prostatic carcinoma cells

Sodium butyrate (NaBT) induces differentiation in several transformed cell lines. The present paper describes the effects of NaBT on some transformation-associated parameters in PC-3, a human prostatic carcinoma cell line. NaBT produces a reversible inhibition of cell proliferation, but anchorage-independent growth is more sensitive than monolayer growth. Soft agarose colonies are reduced by over 50% at 0.1 mM, a concentration that hardly affects growth on solid substrata. Monolayer cells respond to NaBT by spreading and flattening, as demonstrated by a combined light and electron microscopic, morphometric technique. After 4 days' exposure to 2 mM NaBT, the average cell covers an area of substratum that is approximately double that covered by control cells. The average cell volume, however, remains unchanged. This flattening is paralleled by an increase in the number of stress fibers, as seen by fluorescence microscopy. Only minor changes are observed in the microtubule and intermediate filament patterns. While control cells contain very little antifibronectin reactive material, substantial amounts of such material appear upon NaBT treatment. The amount of fibronectin increases up to 100-fold in cells exposed to NaBT. The changes observed correspond to a suppression of properties that are generally associated with the malignant phenotype.