Hydroxymatairesinol, a Novel Enterolactone Precursor With Antitumor Properties From Coniferous Tree (Picea abies)

Lariciresinol is a dietary lignan that accounts for a significant portion of the total phytoestrogen intake from Western foods. Recent epidemiological studies suggest that high dietary intake of lignans and lariciresinol is associated with reduced breast cancer risk. However, no causal relationship between lariciresinol intake and breast cancer development has been established. In this study, we investigated for the first time the effects and possible mechanisms of action of lariciresinol on hormone responsive mammary cancer in vivo in dimethylbenz [a]anthracene induced mammary cancer in rats, and in human MCF-7 breast cancer xenografts in athymic mice. For tumor bearing rats, lariciresinol (3 or 15 mg/kg of body weight) or vehicle was administered p.o. daily for 9 weeks. For E2-maintained ovariectomized athymic mice bearing orthotopic MCF-7 tumors, control diet (AIN-93G) or lariciresinol containing diet (AIN-93G supplemented with 20 or 100 mg of lariciresinol/kg of diet) was administered for 5 weeks. In both models, lariciresinol administration inhibited the tumor growth and tumor angiogenesis. In MCF-7 cells, enterolactone significantly inhibited the E2-stimulated VEGF secretion. Moreover, in MCF-7 xenografts, lariciresinol administration enhanced tumor cell apoptosis and increased estrogen receptor beta expression. Lariciresinol and its further metabolites secoisolariciresinol, enterodiol and enterolactone were found in serum of both rats and athymic mice confirming a similar lignan metabolism pattern as in humans. These findings indicate conceivable importance of dietary lignan lariciresinol in inhibition of breast cancer development.

Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Dietary lariciresinol attenuates mammary tumor growth and reduces blood vessel density in human MCF‐7 breast cancer xenografts and carcinogen‐induced mammary tumors in rats

Saarinen

Wärri

Dings

et al. 2008

“…21,42,43 The intrinsic biologic effects of enterolactone have been attributed to its estrogenic activity, 1 but a recent study did not find any estrogenic or antiestrogenic activity of enterolactone. 44 …”

Section: Enterolactone and Prostate Cancer Riskmentioning

confidence: 99%

Circulating enterolactone and prostate cancer risk: A Nordic nested case‐control study

Stattin

Adlercreutz

Tenkanen³

et al. 2002

“…In vitro, both soy isoflavones and enterolactone have been demonstrated to interact with estrogen receptor (ER) a and b. Soy isoflavones bind and transactivate both ERs with high affinity 5,6 while enterolactone binds weakly to ERs 7 and activate gene expression via ERs at high concentration. 7,8 Isoflavone and lignan-rich diets are reported to have distinct effects on the growth of estrogen responsive tumors in vivo. After estrogen deprivation, SP and its isoflavone genistein have been shown to increase the growth of the MCF-7 tumors in ovariectomized animals, [9][10][11] while no stimulation of MCF-7 tumor growth has been observed when mice were exposed to FS 12 or its mammalian lignan metabolites, enterodiol and enterolactone.…”

mentioning

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

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.