Abstract
This study was to demonstrate by histological grading whether soy protein protects against dimethylbenz[a]anthracene (DMBA) -induced breast tumors in female rats. At 25 days of age, rats were fed diets containing either casein or soy protein. After 25 days on diets, a single dose of DMBA in sesame oil (80 mg/kg) was administered by gavage. All tumors were detected by palpation. The number of tumors per rat was less in soy group than that in casein group at any time point up to 122 days after DMBA administration. Incidence of tumors was less in soy protein group than that in casein group. Casein group had 20% grade I, 60% grade II, and 20% grade III adenocarcinoma. However, the soy group had 100% grade I adenocarcinoma and no aggressive grade II or grade III tumor. There was a delay in the development of tumor in the soy protein group in comparison to the casein group. Again, unlike casein, the soy group had cessation of angiogenesis at several sites of tumor, and reduced levels of angiogenic markers, VEGF and bFGF. Immunohistochemical analysis of the breast tissues did not show any CD-31 positive stain in soy protein group, whereas some CD-31 positive stain was revealed in casein group, which further suggests that soy protein controls angiogenesis. Furthermore, proliferative index as assessed by Ki-67 staining was less in soy protein group than that in casein group. These findings suggest that the soy protein may protect against the development of a more aggressive breast carcinoma.
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Barnes S, Grubbs C, Setchell KDR, Carlson J: Soybeans inhibit mammary tumors in models of breast cancer. Prog Clin Biol Res 1347: 239–253, 1990
Dunn JE: Cancer epidemiology in populations of the United States-with emphasis on Hawaii and California and Japan. Cancer Res 35: 3240–3245, 1975
Kolonel LN: Variability in diet and its relation to risk in ethnic and migrant groups. Basic Life Sci 43: 129–135, 1988
Buell P: Changing incidence of breast cancer in Japanese-American women. J Natl Cancer Inst 51: 1479–1483, 1973
Wu AH, Ziegler RG, Nomura AMY, et al.: Soy intake and risk of breast cancer in Asians and Asian Americans. Am J Clin Nutr 68(suppl): 1437S–1443S, 1998
Adlercreutz H, Mousavi Y, Hockerstedt K: Diet and breast cancer. Acta Oncol 31: 175–181, 1992
Adlercreutz H: Western diet and Western diseases: some hormonal and biochemical mechanisms and associations. Scand J Clin Lab Invest 50(suppl): 3–23, 1990
Hakkak R, Korourian S, Shelnutt SR, et al: Diets containing whey proteins or soy protein isolate protect against 7,12-Dimethylbenz (a) anthracene-induced mammary tumors in female rats. Cancer Epidemiol Biomarkers Prev 9: 113–117, 2000
Troll W, Wiesner R, Shellabarger C, et al.: Soybean diet lowers breast tumor incidence in irradiated rats. Carcinogenesis 1: 469–472, 1980
Kennedy AR: The evidence for soybean products as cancer preventive agents. J Nutr 125: 733S–743S, 1995
Messina MJ, Persky V, Setchell KD, Barnes S: Soy intake and cancer risk: a review of the in vitro and in vivo data. Nutr Cancer 21: 113–131, 1994
McMichael-Phillips DF, Harding C, Morton M, et al.: Effects of soyprotein supplementation on epithelial proliferation in the histologically normal human breast. Am J Clin Nutr 68 (suppl): 1431S–1435S, 1998
Petrakis NL, Barnes S, King EB, et al.: Stimulatory influence of soyprotein isolate on breast fluid secretion in pre and postmenopausal women. Cancer Epidemiol Biomarkers Prev 5: 785–794, 1996
Elston CW, Ellis IO: Pathological prognostic factors in breast cancer. The value of histological grade in breast cancer: experience from a large study with long-term follow up. Histopathology 19: 403–410, 1991
Salvesen HB, Iversen OE, Akslen LA: Prognostic significance of Angiogenesis and Ki-67, p53, and p21 expression: a population-based endometrial carcinoma study. J Clin Oncol 17: 1382–1390, 1999
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 193: 1772–1775, 1951
Russo J, Gustenson BA, Rogers AE, Russo IH, Wellings SR, von Zwietr MH: Comparative study of human and rat mammary tumorigenesis. Lab Invest 62:1–32, 1990
Young S, Hallowes RC: Tumors of the mammary gland. In: Pathology of Tumors in Laboratory Animals. Lyon, France: IARC Scientific Publications 31–86, 1973
Simmen RCM, Eason RR, Till SR, Chatman L, Velarde MC, Geng Y, Korourian S, Badger TM: Inhibition of NMU-induced mammary tumorigenesis by dieatary soy. Cancer Lett 224: 45–52, 2005
Folkman J: What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 82: 4–6, 1989
Zhou JR, Yu L, Mai Z, Blackburn GL: Combined inhibition of estrogen-dependent human breast carcinoma by soy and tea bioactive components in mice. Int J Cancer 108: 8–14, 2003
Fotsis T, Pepper MS, Aktas E, et al.: Flavonoids, dietary-derived inhibitors of cell proliferation and in vitro angiogenesis. Cancer Res 57: 2916–2921, 1997
Belperio JA, Keane MP, Arenberg DA, Addison CL, Ehlert JE, Burdick MD, Strieter RM: CXC chemokines in angiogenesis. J Leukoc Biol 68: 1–8, 2000
Crowther M, Brown NJ, Bishop ET, Lewis CE: Micro-environmental influence on macrophage regulation of angiogenesis in wounds and malignant tumors. J Leukoc Biol 4: 478–490, 2001
Toi M, Bando H, Ogawa T, Muta M, Hornig C, Weich HA: Significance of vascular endothelial growth factor (VEGF)/soluble VEGF receptor-1 relationship in breast cancer. Int J Cancer 98: 14–18, 2002
Gasparini G: Prognostic value of vascular endothelial growth factor in breast cancer. Oncologist 5(Suppl 1): 37–44, 2000
Linderholm B, Lindh B, Tavelin B, Grankvist K, Henriksson R: p53 and vascular-endothelial-growth-factor (VEGF) expression predicts outcome in 833 patients with primary breast carcinoma. Int J Cancer 89: 51–62, 2000
Eppenberger U, Kueng W, Schlaeppi JM, Roesel JL, Benz CC, Mueller H, et al.: Markers of tumor angiogenesis and proteolysis independently define high- and low-risk subsets of node-negative breast cancer patients. J Clin Oncol 16: 3129–3136, 1998
McMahon G: VEGF receptor signaling in tumor angiogenesis. Oncologist 5(Suppl 1): 3–10, 2000
Shibuya M: Structure and function of VEGF/VEGF-receptor system involved in angiogenesis. Cell Struct Funct 26: 25–35, 2001
Gasparini G, Toi M, Gion M, Verderio P, Dittadi R, Hanatani R, et al.: Prognostic significance of vascular endothelial growth factor protein in node-negative breast carcinoma. J Natl Cancer Inst 89: 139–147, 1997
Branham WS, Dial SL, Moland CL, et al.: Phytoestrogens and mycoestrogens bind to the rat uterine estrogen receptor. J Nutr 132: 658–664, 2002
Akiyama T, Ishida J, Knakagawa S, et al.: Genistein, a specific inhibitor of tyrosine-specific protein kinases. J Biol Chem 262: 5592–5595, 1987
Blume-Jensen P, Hunter T. Oncogenic kinase signaling. Nature (Lond) 411: 355–365, 2001
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Mukhopadhyay, S., Ballard, B.R., Mukherjee, S. et al. Beneficial effects of soy protein in the initiation and progression against dimethylbenz [a] anthracene-induced breast tumors in female rats. Mol Cell Biochem 290, 169–176 (2006). https://doi.org/10.1007/s11010-006-9184-9
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DOI: https://doi.org/10.1007/s11010-006-9184-9