Mammalian lignans and genistein decrease the activities of aromatase and 17β-hydroxysteroid dehydrogenase in MCF-7 cells

Brooks, Jennifer; Thompson, Lilian U.

doi:10.1016/j.jsbmb.2005.02.002

Cited by 164 publications

(116 citation statements)

References 47 publications

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“…41 These findings indicate that lignans may have pleiotropic effects in hormone responsive organs depending on the target tissue and hormonal status of the individual and act both as antiestrogen-like or estrogen-like compounds. They may also affect steroidogenesis by inhibiting aromatase, 15,42,43 17b-hydroxysteroid dehydrogenase type 2, 43 and 5a-reductase enzymes 44 as has been demonstrated in in-vitro studies. Lignans may as well act via other non-hormone related mechanisms e.g.…”

Section: Discussionmentioning

confidence: 88%

“…androgens) by adrenal cortex as well as aromatase activity of peripheral tissues are very low; therefore, tumors don't grow unless estrogen or compounds with estrogenic activity are provided. Intact MCF-7 cells have a low aromatase activity, 43 but it is not sufficient to produce enough estrogens even with supplemented androgens to maintain the MCF-7 tumor growth in vivo. 49 Xenografts of MCF-7 cells stably transfected with the human aromatase gene (MCF-7Ca) in ovariectomized, immune-suppressed mice with androgen supplement has been suggested to be a better model to simulate the postmenopausal breast cancer patient, 49 in whom the major source of the hormone is nonovarian tissue.…”

Section: Discussionmentioning

confidence: 99%

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Flaxseed attenuates the tumor growth stimulating effect of soy protein in ovariectomized athymic mice with MCF‐7 human breast cancer xenografts

Saarinen

Power

Chen

et al. 2006

Intl Journal of Cancer

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In several epidemiological studies, a phytoestrogen-rich diet containing lignans and isoflavones is associated with reduced breast cancer risk, but experimental findings are controversial. In postmenopausal mammary cancer xenograft model, flaxseed (FS), a rich source of plant lignans, reduced breast cancer growth, while soy protein (SP), a rich source of isoflavones, enhanced it. The intake of phytoestrogens is increasing particularly among postmenopausal women, emphasizing the importance of elucidating their interactive effects on breast cancer. Our study determined the effect of FS and SP diets, alone and in combination, on the established human breast cancer MCF-7 tumor growth in ovariectomized athymic nude mice. Tumor bearing mice were divided into 4 groups and fed for 25 weeks either the basal diet (BD), or BD supplemented with 10% FS, 20% SP or 10% FS and 20% SP. After estrogen deprivation, FS regressed the tumor size similar to that of control. SP initially regressed the tumors but starting at week 13, the tumors regressed significantly less than in control and 43% of the tumors were regrowing until the end of the experiment and were significantly larger in size than in control. The combination of SP with FS reduced the tumor growth similar to that of control, as suggested also by the reduced tumor cell proliferation index. In conclusion, dietary FS did not stimulate the growth of estrogen responsive MCF-7 cancers in ovariectomized mice, while long-term consumption of SP did. Furthermore, FS reduced the tumor growth stimulating effect of SP to the same level as control, suggesting tumor growth attenuating effect of FS. ' 2006 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Flaxseed attenuates the tumor growth stimulating effect of soy protein in ovariectomized athymic mice with MCF‐7 human breast cancer xenografts

Saarinen

Power

Chen

et al. 2006

Intl Journal of Cancer

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“…In MCF-7 cells, which usually express relatively low levels of aromatase, both END and ENL exhibited aromatase inhibiting activity but END showed a stronger effect. 27 Limited in vivo data, including our own, on the effects of mammalian lignans on tumor growth are in contrast to the in vitro data. In DMBA-induced tumor bearing rats, ENL (10 mg/kg BW) reduced the growth of established mammary tumors.…”

Section: Discussionmentioning

confidence: 89%

Mammalian lignans enterolactone and enterodiol, alone and in combination with the isoflavone genistein, do not promote the growth of MCF‐7 xenografts in ovariectomized athymic nude mice

Power

Saarinen

Chen

et al. 2005

Intl Journal of Cancer

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This study determined the effect of the mammalian lignans enterolactone (ENL) and enterodiol (END) alone and in combination with the isoflavone genistein (GEN) on the growth of MCF-7 tumors in ovariectomized nude mice. Ovariectomized athymic nude mice with established MCF-7 tumors were fed a basal diet (AIN-93G) and divided into 5 groups that received daily subcutaneous injections (10 mg/kg body weight (BW)) of ENL, END, GEN, a mixture of these compounds (MIX), or vehicle as a negative control for 22 weeks. A positive control group was implanted with an estradiol pellet in order to establish an estrogenic tumor growth response. In the ENL-and END-treated mice, palpable tumors regressed significantly by 91 and 83%, respectively, resulting in final tumors that were similar to the negative control tumors. However, tumor cell apoptosis was significantly enhanced by the lignans. In the GEN-treated mice, tumors initially regressed significantly by 64% but regression ceased following prolonged treatment, resulting in final tumors that were significantly larger compared to negative control, ENL-, and END-treated mice, in part by increasing tumor cell proliferation. The MIX treatment significantly regressed palpable tumors by 87% similar to negative control group, with no effects on tumor cell apoptosis or proliferation. The isoflavone GEN alone promoted the growth of established MCF-7 human breast cancer xenografts after prolonged treatment while the mammalian lignans ENL and END did not. When these phytoestrogens were given in combination, no tumor growth-promoting effects were observed. ' 2005 Wiley-Liss, Inc.

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“…However, second and third generation descendants of women who migrated from Asia to Western countries have breast cancer risks similar to those of women in the host country, suggesting that lifestyle and dietary habits, and not genetic factors explain the low breast cancer risk of women in Asia [30,34,35]. Furthermore, epidemiologic studies have detected an association between phytoestrogen consumption, phytoestrogen levels in plasma and urine, and reduced risk of breast cancer [28,36]. Studies using animal models of breast cancer have shown that a number of phytoestrogens, including quercetin, reduce the incidence and inhibit the development of N-methyl-N-nitrosourea (NMU) and DMBA-induced mammary carcinogenesis in rats [37][38][39][40][41][42][43].…”

Section: Introductionmentioning

confidence: 99%

Preferential induction of cytochrome P450 1A1 over cytochrome P450 1B1 in human breast epithelial cells following exposure to quercetin

Mense

Chhabra

Bhat

2008

The Journal of Steroid Biochemistry and Molecular Biology

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Estrogen metabolism is suggested to play an important role in estrogen-induced breast carcinogenesis. Epidemiologic studies suggest that diets rich in phytoestrogens are associated with a reduced risk of breast cancer. Phytoestrogens are biologically-active plant compounds that structurally mimic 17β-estradiol (E 2 ). We hypothesize that phytoestrogens, may provide protection against breast carcinogenesis by altering the expression of estrogen-metabolizing enzymes cytochrome P450 1A1 (Cyp1A1) and 1B1 (Cyp1B1). Cyp1A1 and Cyp1B1 are responsible for the metabolism of E 2 to generate 2-hydroxyestradiol (2-OHE 2 ) and 4-hydroxyestradiol (4-OHE 2 ), respectively. Studies suggest that 2-OHE 2 and 2-methoxyestradiol may protect against breast carcinogenesis, while 4-OHE 2 is carcinogenic in rodent models. Thus, agents that increase the metabolism of E 2 by Cyp1A1 to produce 2-OHE 2 may have chemoprotective properties. The human immortalized non-neoplastic breast cell line MCF10F was treated with quercetin at 10 and 50 µM concentrations for time-points ranging from 3 to 48 hours. Total RNA and protein were isolated. Real-time PCR was used to measure the expression of Cyp1A1 and Cyp1B1 mRNA. Quercetin treatment produced differential regulation of Cyp1A1 and Cyp1B1 mRNA expression in a time-and dose-dependent manner. Treatment with 10 and 50 µM doses of quercetin produced 6-and 11-times greater inductions of Cyp1A1 mRNA over Cyp1B1 mRNA, respectively. Furthermore, quercetin dramatically increased Cyp1A1 protein levels and only slightly increased Cyp1B1 protein levels in MCF10F cells. Thus, our data suggest that phytoestrogens may provide protection against breast cancer by modulating expression of estrogen-metabolizing genes such that production of the highly carcinogenic estrogen metabolite 4-OHE 2 by Cyp1B1 is reduced and the production of the less genotoxic 2-OHE 2 by Cyp1A1 is increased.

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Mammalian lignans and genistein decrease the activities of aromatase and 17β-hydroxysteroid dehydrogenase in MCF-7 cells

Cited by 164 publications

References 47 publications

Flaxseed attenuates the tumor growth stimulating effect of soy protein in ovariectomized athymic mice with MCF‐7 human breast cancer xenografts

Flaxseed attenuates the tumor growth stimulating effect of soy protein in ovariectomized athymic mice with MCF‐7 human breast cancer xenografts

Mammalian lignans enterolactone and enterodiol, alone and in combination with the isoflavone genistein, do not promote the growth of MCF‐7 xenografts in ovariectomized athymic nude mice

Preferential induction of cytochrome P450 1A1 over cytochrome P450 1B1 in human breast epithelial cells following exposure to quercetin

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