Mammalian lignans enterolactone and enterodiol, alone and in combination with the isoflavone genistein, do not promote the growth of MCF-7 xenografts in ovariectomized athymic nude mice

Int J Cancer. 2006 Mar 1;118(5):1316-20. doi: 10.1002/ijc.21464.


This study determined the effect of the mammalian lignans enterolactone (ENL) and enterodiol (END) alone and in combination with the isoflavone genistein (GEN) on the growth of MCF-7 tumors in ovariectomized nude mice. Ovariectomized athymic nude mice with established MCF-7 tumors were fed a basal diet (AIN-93G) and divided into 5 groups that received daily subcutaneous injections (10 mg/kg body weight (BW)) of ENL, END, GEN, a mixture of these compounds (MIX), or vehicle as a negative control for 22 weeks. A positive control group was implanted with an estradiol pellet in order to establish an estrogenic tumor growth response. In the ENL- and END-treated mice, palpable tumors regressed significantly by 91 and 83%, respectively, resulting in final tumors that were similar to the negative control tumors. However, tumor cell apoptosis was significantly enhanced by the lignans. In the GEN-treated mice, tumors initially regressed significantly by 64% but regression ceased following prolonged treatment, resulting in final tumors that were significantly larger compared to negative control, ENL-, and END-treated mice, in part by increasing tumor cell proliferation. The MIX treatment significantly regressed palpable tumors by 87% similar to negative control group, with no effects on tumor cell apoptosis or proliferation. The isoflavone GEN alone promoted the growth of established MCF-7 human breast cancer xenografts after prolonged treatment while the mammalian lignans ENL and END did not. When these phytoestrogens were given in combination, no tumor growth-promoting effects were observed. (c) 2005 Wiley-Liss, Inc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / pharmacology
  • Animals
  • Apoptosis / drug effects
  • Body Weight / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Therapy, Combination
  • Feeding Behavior / drug effects
  • Genistein / pharmacology*
  • Humans
  • Lignans / pharmacology*
  • Mice
  • Mice, Nude
  • Neoplasms / pathology*
  • Ovariectomy
  • Xenograft Model Antitumor Assays


  • Lignans
  • 2,3-bis(3'-hydroxybenzyl)butane-1,4-diol
  • Genistein
  • 4-Butyrolactone
  • 2,3-bis(3'-hydroxybenzyl)butyrolactone