Both epidemiological and experimental evidence is accumulating to show that a
lignan-rich diet may reduce the risk of human
breast cancer. Possible anti-
cancer effects of dietary
lignans on
hepatomas or
hepatoma cells have not been the topic of earlier studies. In the present study, we examined the effect of
7-hydroxymatairesinol (HMR) and its mammalian metabolite,
enterolactone (ENL), on AH109A
hepatoma cell proliferation and invasion in vitro. HMR and ENL inhibited the proliferation and invasion of AH109A
hepatoma cells in vitro. The 50% inhibitory concentration (IC50) of
hepatoma cell proliferation was lower for ENL (10 microM) than HMR (> 200 microM). Likewise, IC50 of
hepatoma cell invasion was lower for ENL (9 microM) than HMR (144 microM). ENL suppressed
hepatoma cell proliferation by accumulating cells in G1 phase and elongating doubling time of these cells, and by increasing the rate of apoptosis. Subsequently, we investigated in vivo the effect of dietary HMR and ENL on growth and
metastasis of AH109A
hepatomas in rats. Both of these compounds reduced the growth and
metastasis of solid AH109A
hepatomas in rats. These in vitro and in vivo findings suggest that HMR has inhibitory activities on
tumor growth and
metastasis in the
hepatoma-bearing rats, and that this anti-
tumor effect is mediated at least partially by ENL, a metabolite of HMR.