Dietary Soy Isoflavones and Estrone Protect Ovariectomized ERKO and Wild-Type Mice from Carcinogen-Induced Colon Cancer

Author: Ju-Yuan Guo, Xiaosong Li, Jimmy D. Browning, Jr., George E. Rottinghaus, Dennis B. Lubahn, Andreas Constantinou, Maurice Bennink and Ruth S. MacDonald
Publication: Journal of Nutrition:179-182, January 2004

In the US, colon cancer is the third most common form of cancer. The World Cancer Research Fund and American Institute for Cancer Research concluded that the risk of colon cancer could be reduced by increased intake of vegetables and that the consumption of alcohol and red meat increased the risk of colon cancer. Epidemiological studies indicate that consumption of soy is weakly associated with reduced colon cancer risk. It is known that estrogen increases colon cancer risk and that the conversion of estradiol to estrone may reduce this risk. Soy isoflavone are known to bind to estrogen receptors, with a higher affinity for beta estrogen receptors. Colon cancer is normally not considered as a hormone-dependant cancer but there are indications that high dose oral contraceptives, containing exogenous steroid hormones, protected the women from colon cancer. In the US soy consumption increased after the approval of the soy protein health claim by the FDA, stating that consuming daily 25 g of soy protein could reducing cardiovascular diseases. Menopausal women are using soy extracts containing isoflavones as an alternative to hormone replacement therapy.

The purpose of this study was to investigate if isoflavones or estrone could reduce the colon cancer risk by interfering with the estrogen receptor. This study was carried out on mice (ovariectomized and wild type) which were divided in 5 groups, based on protein source of their diet:

  • casein
  • soy protein without isoflavones
  • soy protein and genistein
  • soy protein commercial soy extract (NovaSoy)
  • soy protein with estrone.

Colon tumors were chemically induced by the carcinogen azoxymethane. Mice fed soy protein diets, regardless of the addition of estrone or isoflavones, had lower colon tumor burden and multiplicity compared with mice fed casein protein. The incidence of colon tumors incidence was lower in mice fed the soy protein with estrone as compared with those fed with casein protein or soy protein without isoflavones. Mice fed soy protein with NovaSoy had a lower tumor incidence than mice fed with casein. Genistein had no influence on tumor incidence. The addition of NovaSoy to the soy protein reduced tumor incidence compared with casein-fed mice. Soy protein significantly reduced relative colon weight, tumor burden and multiplicity. The protective role of soy protein soy protein may be explained by reduction in cell proliferation, but the components which are responsible for this action are not yet identified. Although al diets contain the same amounts of dietary fiber it could be that the structure of soy fiber had another influence on the gut microflora. The phytate levels were also the same in all diets but the added phytate may have different physiochemical properties.

The researchers concluded that soy protein and NovaSoy protect mice from colon cancer and that estrone further reduces colon tumorigenesis in mice. The findings that estrone reduced colon tumorigenesis confirms evidence from the Women’s Health Initiative that hormone replacement therapy may be protective of colon cancer and provides a new approach for the prevention of colon cancer.