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Nutrition and Cancer

Lignans Are Involved in the Antitumor Activity of Wheat Bran in Colon Cancer SW480 Cells^1,2

Hongyan Qu, Ronald L. Madl^*, Dolores J. Takemoto, Richard C. Baybutt and Weiqun Wang³

Department of Human Nutrition, ^* Department of Grain Science, and Department of Biochemistry, Kansas State University, Manhattan, KS 66506

³To whom correspondence should be addressed. E-mail: wwang{at}ksu.edu.

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 µmol/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 µmol/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.

KEY WORDS: • lignans • wheat bran • SW480 colon cancer cells • cell cycle arrest • apoptosis

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