BUTYRATE INHIBITS COLON-CARCINOMA CELL-GROWTH THROUGH 2 DISTINCT PATHWAYS

Background, Dietary fiber and the resultant increase in colonic butyra te levels protect against colon carcinogenesis. Previous studies have shown that p21 and histone hyperacetylation are important in basal gro wth inhibition by butyrate. This study was designed to elucidate other mechanisms underlying the butyrate effects on cell growth. Methods. H T-29 colon carcinoma cells (standard medium or medium lacking serum) w ere treated with sodium butyrate (NaBu), epidermal growth factor (EGF) , or both. Northern blot analyses were performed with cDNA probes spec ific for c-fos, c-jun, and actin. Cell growth was measured by H-3-thym idine incorporation. Enzyme-linked immunosorbent assay (ELISA) was use d to quantify EGF receptor levels. Results, Butyrate and serum starvat ion (SS) both induced a cell cycle withdrawal by 24 hours. In response to EGF treatment, SS cells exhibited a growth spurt and induced c-fos and jun proto-oncogene expression, whereas butyrate-treated cells exh ibited minimal growth response to EGF. This relative unresponsiveness to EGF in butyrate-treated cells corresponded to a dramatic decline in EGF receptor levels when compared to untreated controls. Conclusions. Butyrate appears to inhibit colon cancer cell growth by true mechanis ms, one involving histone hyperacetylation and p21 induction and the o ther related to impaired EGF-responsiveness.