Submitted on September 6, 2002
Accepted on January 21, 2003
Upregulation of activin A gene by butyrate in human colon cancer cell lines
Kei Sonoyama1*, Pimara Pholnukulkit1, Masahiko Toyoda1, Suriya Rutatip1, and Takanori Kasai1
1 Graduate School of Agriculture, Hokkaido University, Sapporo, Hokkaido, Japan
* To whom correspondence should be addressed. E-mail: ksnym{at}chem.agr.hokudai.ac.jp.
Activin A has been reported to play a role in the progression of colorectal cancer. Since 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 activin A gene was upregulated by sodium butyrate in human colon cancer cell lines HT-29 and Caco-2 in concentration- and time-dependent manner. However, activin A gene did not respond to sodium butyrate in human normal colonic cell line FHC, rat normal intestinal cell line IEC-6 and 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. Assuming that activin A promotes colorectal cancer spread as a paracrine factor, the present findings suggest that butyrate could act as a tumor promoter in some circumstances.
