Short chain fatty acids differentially modulate cellular phenotype and c-myc protein levels in primary human nonmalignant and malignant colonocytes

• Published in: Digestive diseases and sciences Vol. 46; no. 1; pp. 96 - 105
• Main Authors: EMENAKER, Nancy J, BASSON, Marc D
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 2001; Springer Nature B.V
• Subjects: Aged; Alkaline Phosphatase - analysis; Biological and medical sciences; Butyrates - pharmacology; Cell Separation; Cell Survival; Cells, Cultured; Colon - cytology; Colon - pathology; Colonic Neoplasms - pathology; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases - analysis; DNA - biosynthesis; DNA, Neoplasm - biosynthesis; Fatty Acids, Volatile - pharmacology; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Male; Medical sciences; Phenotype; Proto-Oncogene Proteins c-myc - analysis; Stimulation, Chemical; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Thymidine - metabolism; Tumors; Human; Cell culture; Short chain; Nutrition; Biosynthesis; Malignant tumor; Fatty acids; Biological activity; Colonic disease; Phenotype; Digestive diseases; Intestinal disease; Epithelial cell; Colon; Comparative study
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1023/A:1005661809250

Short chain fatty acids may protect colonic mucosa against neoplastic transformation by modulating colonocyte phenotype, DNA synthesis, and c-myc levels. To test this hypothesis, nonmalignant and malignant human colonocytes were isolated from surgical specimens and treated with 10 mM acetate, propionate, or butyrate. Markers of cellular phenotype, DNA synthesis, and c-myc protein levels were assayed by alkaline phosphatase and dipeptidyl dipeptidase IV activities, [3H]thymidine labeling, and western blotting, respectively. Butyrate, in particular, exerted discordant effects on alkaline phosphatase (P < 0.05), and c-myc levels (P < 0.05, N > or = 6) in nonmalignant and malignant human colonocytes. DPDD was unaffected by any of the short chain fatty acids tested. [3H]Thymidine labeling was differentially stimulated by short chain fatty acids in both cell types and greater DNA synthesis rates were observed in malignant colonocytes (P < 0.005, N = 16). These data suggest that in vitro, butyrate, in particular, may differentially modulate phenotype, DNA synthesis, and c-myc in nonmalignant and malignant human colonocytes.