Vol. 284, Issue 6, G989-G995, June 2003
Upregulation of activin A gene by butyrate in human colon
cancer cell lines
Kei
Sonoyama,
Pimara
Pholnukulkit,
Masahiko
Toyoda,
Suriya
Rutatip, and
Takanori
Kasai
Laboratory of Food Biochemistry, Division of Applied Bioscience,
Graduate School of Agriculture, Hokkaido University, Sapporo
060-8589 Japan
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.
cancer; transforming growth factor-
; dietary fiber
