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Soy Protein Isolates Inhibited Growth of Estrogen‐Dependent Human Breast Tumors in a Clinically Relevant Orthotopic Breast Tumor Model
Author(s) -
Zhou JinRong,
Singh Ajita,
Liu Derek,
Blackburn George
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a853-b
Subject(s) - estrogen , breast cancer , soy protein , estrogen receptor , isoflavones , breast tumor , mammary tumor , medicine , casein , animal model , endocrinology , cancer , biology , oncology , pathology , food science
Epidemiological investigation has suggested an inverse association between soy consumption and risk of breast cancer. Experimental studies using different animal models and soy products, however, have generated controversial results. Our previous studies have demonstrated that estrogen‐maintained MCF‐7 tumor animal model is clinically relevant to the progression of estrogen‐dependent breast cancer in women. We evaluated the effects of soy protein isolates (SPI) on MCF‐7 tumor growth in this animal model. Female SCID mice (n=24/group) were randomly assigned into the experimental groups and consumed one of the experimental diets for two weeks before sc implantation of estrogen pellets: (i) Control: AIN‐93G, (ii) Isoflavone‐Depleted SPI (IDSPI): AIN‐93G with IDSPI (20% of the diet) in place casein, and (iii) High Isoflavone‐containing SPI (HISPI): AIN‐93G with HISPI (20% of the diet) in place casein, providing 0.54g isoflavone aglycones/kg diet. Mice were then implanted with MCF‐7 cells into the mammary fat pad and the mice continued to the corresponding diets throughout the experiment. Tumor volumes were measured weekly. Eight weeks after tumor was developed, the study was terminated, and tumors were harvested for biomarker determination. Mice treated with the IDSPI or HISPI diet had reduced tumor growth, compared with the control, and the tumor growth reduction started to show statistical significance 5 weeks after tumor was developed. At week 8, the tumor volumes in the IDSPI and HISPI groups were reduced by 79% (P<0.005) and 49% (P=0.08), respectively, compared with the control. The in vivo mechanistic studies indicate that SPI inhibited estrogen‐dependent breast tumor growth by targeting multiple pathways involving tumor cell proliferation, apoptosis and tumor angiogenesis.