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The Effect Of Flaxseed And Soy, and their phytoestrogens, On MCF‐7 Tumor Growth Biomarkers In Ovariectomized Athymic Nude Mice
Author(s) -
Power Krista,
Saarinen Niina,
Chen Jian Min,
Thompson Lilian U
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.lb103-b
Subject(s) - phytoestrogens , cyclin d1 , apoptosis , estrogen receptor , ovariectomized rat , genistein , enterolactone , cell growth , chemistry , mcf 7 , endocrinology , cancer research , medicine , estrogen , cancer , cancer cell , cell cycle , biology , breast cancer , biochemistry , human breast
Combining flaxseed (FS) and soy protein isolate (SPI), or their respective phytoestrogens (PEs), lignans enterolactone (ENL) or enterodiol (END) and isoflavone genistein (GEN), can more effectively reduce the growth of estrogen receptor (ER) positive human breast cancer in ovariectomized mice (simulate postmenopausal situation) than SPI or GEN alone. This study analyzed tumor growth biomarkers with specific focus on signaling pathways involved in cell proliferation and apoptosis. Mice with established MCF‐7 tumors were fed a basal diet (BD), 20%SPI, 10%FS, or 20%SPI + 10%FS for 25 weeks. Tumors were analyzed by immunohistochemistry for proliferation (Ki67 labeling index (LI)), ERα, cyclin D1, apoptosis, and pAkt. SPI enhanced Ki67 LI, ERα, and cyclin D1. SPI also enhanced apoptosis by inhibiting pAkt, but its effects on proliferation were stronger, leading to enhanced tumor growth. FS alone did not alter expression of proteins measured, however, when combined with SPI, a reduction in Ki67 LI, and an attenuation of cyclin D1 were observed with no effect on ERα, compared to SPI alone. The combination also enhanced apoptosis, however, a non‐significant reduction in pAkt was observed. Using the same study model, GEN, like SPI, enhanced Ki67, ERα, and cyclin D1, while the lignans did not; however, its effects were attenuated when combined with the lignans. This indicates that like SPI, the tumor promoting effects of GEN were induced by an increase in cell proliferation mediated by the ER. Since combining lignans or FS with GEN or SPI reduces these effects, it may be better to consume PEs in combination under postmenopausal situation. (supported by NSERC)