Archer S, Meng S, Wu J, Johnson J, Tang R, Hodin R
Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass 02215, USA.
Surgery. 1998 Aug;124(2):248-53.
Dietary fiber and the resultant increase in colonic butyrate levels protect against colon carcinogenesis. Previous studies have shown that p21 and histone hyperacetylation are important in basal growth inhibition by butyrate. This study was designed to elucidate other mechanism underlying the butyrate effects on cell growth.
HT-29 colon carcinoma cells (standard medium or medium lacking serum) were treated with sodium butyrate (NaBu), epidermal growth factor (EGF), or both. Northern blot analyses were performed with cDNA probes specific for c-fos, c-jun, and actin. Cell growth was measured by 3H-thymidine incorporation. Enzyme-linked immunosorbent assay (ELISA) was used to quantify EGF receptor levels.
Butyrate and serum starvation (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 c-jun proto-oncogene expression, whereas butyrate-treated cells exhibited 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.
Butyrate appears to inhibit colon cancer cell growth by two mechanisms, one involving histone hyperacetylation and p21 induction and the other related to impaired EGF-responsiveness.
