Hydroxymatairesinol and Its Mammalian Metabolite Enterolactone Reduce the Growth and Metastasis of Subcutaneous AH109A Hepatomas in Rats

Abstract

: 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 (IC 50 ) of hepatoma cell proliferation was lower for ENL (10 μ M) than HMR (> 200 μ M). Likewise, IC 50 of hepatoma cell invasion was lower for ENL (9 μ M) than HMR (144 μ M). ENL suppressed hepatoma cell proliferation by accumulating cells in G 1 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.