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Beneficial effects of soy protein in the initiation and progression against dimethylbenz [a] anthracene-induced breast tumors in female rats

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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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References

  1. 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

    Google Scholar 

  2. Dunn JE: Cancer epidemiology in populations of the United States-with emphasis on Hawaii and California and Japan. Cancer Res 35: 3240–3245, 1975

    PubMed  CAS  Google Scholar 

  3. Kolonel LN: Variability in diet and its relation to risk in ethnic and migrant groups. Basic Life Sci 43: 129–135, 1988

    PubMed  CAS  Google Scholar 

  4. Buell P: Changing incidence of breast cancer in Japanese-American women. J Natl Cancer Inst 51: 1479–1483, 1973

    PubMed  CAS  Google Scholar 

  5. 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

    Google Scholar 

  6. Adlercreutz H, Mousavi Y, Hockerstedt K: Diet and breast cancer. Acta Oncol 31: 175–181, 1992

    PubMed  CAS  Google Scholar 

  7. Adlercreutz H: Western diet and Western diseases: some hormonal and biochemical mechanisms and associations. Scand J Clin Lab Invest 50(suppl): 3–23, 1990

    Google Scholar 

  8. 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

    PubMed  CAS  Google Scholar 

  9. Troll W, Wiesner R, Shellabarger C, et al.: Soybean diet lowers breast tumor incidence in irradiated rats. Carcinogenesis 1: 469–472, 1980

    PubMed  CAS  Google Scholar 

  10. Kennedy AR: The evidence for soybean products as cancer preventive agents. J Nutr 125: 733S–743S, 1995

    PubMed  CAS  Google Scholar 

  11. 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

    Article  PubMed  CAS  Google Scholar 

  12. 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

    Google Scholar 

  13. 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

    PubMed  CAS  Google Scholar 

  14. 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

    PubMed  CAS  Google Scholar 

  15. 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

    PubMed  CAS  Google Scholar 

  16. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 193: 1772–1775, 1951

    Google Scholar 

  17. 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

    Google Scholar 

  18. Young S, Hallowes RC: Tumors of the mammary gland. In: Pathology of Tumors in Laboratory Animals. Lyon, France: IARC Scientific Publications 31–86, 1973

  19. 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

    Google Scholar 

  20. Folkman J: What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 82: 4–6, 1989

    Google Scholar 

  21. 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

    Article  CAS  Google Scholar 

  22. 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

    PubMed  CAS  Google Scholar 

  23. 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

    PubMed  CAS  Google Scholar 

  24. 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

    Google Scholar 

  25. 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

    Article  PubMed  CAS  Google Scholar 

  26. Gasparini G: Prognostic value of vascular endothelial growth factor in breast cancer. Oncologist 5(Suppl 1): 37–44, 2000

    Google Scholar 

  27. 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

    Google Scholar 

  28. 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

    PubMed  CAS  Google Scholar 

  29. McMahon G: VEGF receptor signaling in tumor angiogenesis. Oncologist 5(Suppl 1): 3–10, 2000

    Google Scholar 

  30. Shibuya M: Structure and function of VEGF/VEGF-receptor system involved in angiogenesis. Cell Struct Funct 26: 25–35, 2001

    Article  PubMed  CAS  Google Scholar 

  31. 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

    Article  PubMed  CAS  Google Scholar 

  32. Branham WS, Dial SL, Moland CL, et al.: Phytoestrogens and mycoestrogens bind to the rat uterine estrogen receptor. J Nutr 132: 658–664, 2002

    PubMed  CAS  Google Scholar 

  33. Akiyama T, Ishida J, Knakagawa S, et al.: Genistein, a specific inhibitor of tyrosine-specific protein kinases. J Biol Chem 262: 5592–5595, 1987

    PubMed  CAS  Google Scholar 

  34. Blume-Jensen P, Hunter T. Oncogenic kinase signaling. Nature (Lond) 411: 355–365, 2001

    Article  CAS  Google Scholar 

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Correspondence to Salil K. Das.

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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

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