Long-term feeding of field bean protein containing protease inhibitors suppresses virus-induced mammary tumors in mice

Protease inhibitors (PIs) of synthetic, bacterial or soybean origin have been shown to suppress carcinogen or radiation-induced rat mammary carcinogenesis. We report, for the first time, the effect of year-long feeding of Field bean meal, a rich source of PIs with a 24% protein content, at different protein levels in the diet, on mouse mammary tumor virus (MMTV)-induced mammary tumorigenesis in C3H/Jax mice. Weanling female mice were randomized and divided into groups and fed chow or chow with 2%, 4%, 8% FB protein (FBP) or autoclaved 2% FBP (AFBP) until 49 weeks and the incidence of mammary tumors was recorded until 58 weeks when they were sacrificed. Mice fed 2% FBP showed significant (P<0.001) reduction (68%) in tumor incidence and delay (P<0.02) in tumor appearance compared to controls. This suppressive effect on mammary tumorigenesis increased with increased FBP intake with values of tumor suppression being 75% and 81% in mice groups fed 4% and 8% FBP, respectively. Incidentally, the tumors appeared earlier (P<0.05) in the 8% FBP-treated mice compared to other groups. Moreover, this suppressive effect on mammary tumorigenesis was related to the PI activity of the FB meal, since mice fed 2% AFBP showed no reduction in tumor incidence. Heat treatment, which had destroyed the PI activity, apparently did not affect other chemopreventive agents known to be present in plant material. This possibility is supported by our observation that prolonged feeding of 2% FBP or 2% AFBP increased the liver glutathione content of mice, suggesting the presence of a highly heat-stable factor, other than PIs, in the FBP, which brought about this elevation. Further, while 2% or 4% FBP- and 2% AFBP- treated mice showed no adverse growth effects, only the 8% FBP-fed group showed a significant lower growth curve compared to control mice, with some of them showing pancreatic lesions.