Butyrate inhibits colon carcinoma cell growth through two distinct pathways.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass 02215, USA.
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Archer
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Meng
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Wu
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Johnson
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Tang
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Hodin
D000199:Actins / Q000235:genetics; D001798:Blood Proteins / Q000494:pharmacology; D015152:Blotting, Northern; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000032:analysis / Q000502:physiology; D019073:HT29 Cells / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis
D000199:Actins; D001798:Blood Proteins; D002087:Butyrates; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D020148:Butyric Acid; D004815:Epidermal Growth Factor; D066246:ErbB Receptors