Control of Initiation and Aggressiveness of DMBA‐Induced Breast Cancer in Rats by Dietary Consumption of Hinute‐AM.

Abstract

We reported earlier that the consumption of soy protein controlled not only the proliferation of dimethylbenz [a] anthracene (DMBA)‐induced breast cancer in rats but also its aggressiveness. Soy protein is hydrolyzed in the gut to small peptides which are easily absorbed and are involved in various cellular functions. Fuji Oil Company, Osaka, Japan, has commercially marketed a soy protein hydrolysate, termed Hinute‐AM, composed of primarily di‐ and tripeptides, to be used as a health food, and it has anti‐inflammatory property. The purpose of the present study was to investigate whether dietary intake of Hinute‐AM can delay the development of DMBA‐induced breast cancer and its aggressiveness in rats. For this study, we obtained 22‐days old female Sprague Dawley rats from Charles River (Wilmington, MA). Animals were divided into 5 groups, each containing 5 animals. Group 1 received standard AIN‐76A diet (Envigo – Teklad Diets, Madison, WI) containing 20% casein and 0% Hinute‐AM; Group 2 received the same diet containing 15% casein + 5% Hinute‐AM; Group 3 received the same diet, but containing 10% casein + 10% Hinute‐AM; Group 4 received the same diet but containing 5% casein + 15% Hinute‐AM; and Group 5 received the same diet but containing 0% casein + 20% Hinute‐AM. For induction of mammary tumors, all groups received a single intragastric administration of DMBA (Sigma Chemical Co., St. Louis) dissolved in sesame oil (80 mg/kg b.wt.) at 50 days of age. At 120 days post DMBA injection, the animals were euthanized by CO2 asphyxiation. All tumors were weighed and measured for volume, and a section of tumor was subjected to histological grading by a certified pathologist. Our preliminary data revealed that replacement of casein by Hinute‐AM as a source of dietary protein caused a dose‐dependent delay in the development of breast tumor, decrease in breast cancer incidence, a decrease in tumor volume, and tumor grade.Support or Funding InformationThis work was supported by grants from Fuji Oil Company, Osaka, Japan and by the Meharry Translational Research Center grant NIH 5U54MD007593