Upregulation of activin A gene by butyrate in human colon cancer cell lines.
Activin A has been reported to play a role in the progression of colorectal cancer. Because dietary fiber protects against colorectal cancer, we hypothesized that butyrate, a fermentation product of dietary fiber, may affect the expression of activin A in colon cancer cells. Semiquantitative RT-PCR demonstrated that the activin A gene was upregulated by sodium butyrate in the human colon cancer cell lines HT-29 and Caco-2 in a concentration- and time-dependent manner. However, the activin A gene did not respond to sodium butyrate in the human normal colonic cell line FHC, rat normal intestinal epithelial cell (IEC) line IEC-6, and the explant of rat colon. Flow cytometry and agarose gel electrophoresis of genomic DNA revealed that cell cycle arrest and apoptosis were induced by sodium butyrate but not exogenous activin A in HT-29 cells, indicating that activin A could not act as an autocrine factor in colon cancer cells. By assuming that activin A promotes colorectal cancer spread as a paracrine factor, our findings suggest that butyrate could act as a tumor promoter in some circumstances.
Sonoyama
Kei
K
Laboratory of Food Biochemistry, Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University, Sapporo 060-8589 Japan. ksnym@chem.agr.hokudai.ac.jp
Pholnukulkit
Pimara
P
Toyoda
Masahiko
M
Rutatip
Suriya
S
Kasai
Takanori
T
D028341:Activins / Q000235:genetics*; D000818:Animals; D002087:Butyrates / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D003110:Colonic Neoplasms / Q000235:genetics*; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D028322:Inhibin-beta Subunits / Q000235:genetics*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects*
D002087:Butyrates; D006877:Hydroxamic Acids; D012333:RNA, Messenger; C422405:activin A; D028341:Activins; C012589:trichostatin A; D028322:Inhibin-beta Subunits