Wheat bran was shown to provide protection against
colorectal cancer in human intervention and animal studies. Our recent study showed, however, that antitumor activities of
wheat bran from various wheat cultivars differed significantly even when wheat fiber was equal in diets. We hypothesized that
phytochemical lignans in
wheat bran may account for the differences among wheat cultivars in
cancer prevention. The concentration of a major
lignan,
secoisolariciresinol diglycoside, was determined by HPLC in 4 selected wheat cultivars (i.e., Madison, Ernie, Betty, and Arapahoe). The
lignan concentrations and their antitumor activities, previously determined in APC-Min mice, were correlated (r = 0.73, P < 0.02). The
cancer preventive mechanisms of 2 prominent
lignan metabolites (
enterolactone and
enterodiol) were further studied in human
colonic cancer SW480 cells. Treatment with
enterolactone and
enterodiol, alone or in combination, at 0-40 micromol/L resulted in dose- and time-dependent decreases in cell numbers. Although the cytotoxicity as measured by
trypan blue staining in adherent cells was not affected,
DNA flow cytometric analysis indicated that the treatments induced cell cycle arrest at the S-phase. Western blot analysis for
cyclin A, a required
protein for S/G2 transition, showed that the
cyclin A protein levels decreased
after treatment with
enterodiol or the combination of
enterolactone and
enterodiol at 40 micromol/L for 72 h. Apoptosis analysis by the
terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay showed an increased percentage of apoptotic cells in the floating cells after
enterodiol alone or combined treatments. These results suggest for the first time that
lignans may contribute, at least in part, to the
cancer prevention by
wheat bran observed in APC-Min mice. Inhibition of
cancer cell growth by
lignan metabolites seems to be mediated by
cytostatic and apoptotic mechanisms.