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

Abstract

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.

Inhibition of Akt signaling by the lignan matairesinol sensitizes prostate cancer cells to TRAIL-induced apoptosis

“…As it is well documented that plant lignans also have potent antitumorigenic activity with minimal side effects (Thompson et al, 1996;Bylund et al, 2005;Saarinen et al, 2008), we tested whether this activity could involve sensitization to death receptor signaling. A number of closely related lignans ( Figure 1a) were tested in a non-toxic concentration for their capacity to sensitize LNCaP prostate cancer cells to TRAIL receptor-mediated apoptosis in the prescence or absence of androgen.…”

“…It has been shown that lignans inhibit proliferation and are cytotoxic to prostate cancer cell lines (Lin et al, 2001, Chen et al, 2007. Moreover, lignans can prevent tumor growth and induce apoptosis in vivo in prostate cancer xenografts or chemically induced mammary tumors (Bylund et al, 2005;Saarinen et al, 2008;Thompson et al, 1996) and can also reduce experimental metastasis (Li et al, 1999). Plant-derived lignans, such as matairesinol (MAT), are metabolized by mammalian gut microflora resulting in enterolactone (ENL) or enterodiol (Axelson et al, 1982).…”

Plant Polyphenols and Tumors: From Mechanisms to Therapies, Prevention, and Protection Against Toxicity of Anti-Cancer Treatments

“…exhibited strong cytotoxicity against a variety of cancer cell lines in vitro, which correlated positively with the number of O-methyl groups in the molecule [233]. Experimental data have shown that some plant lignans were effective against tumor growth and tumor-associated angiogenesis exclusively in hormone responsive mammary cancer [234,235] and not in hormone irresponsive intestinal tumors [236]. Moreover, the number and size of intestinal tumors increased significantly in mice fed with matairesinol [236].…”

Non-wood Forest Products Based on Extractives- A New Opportunity for Canadian Forest Industry Part 2- Softwood Forest Species

“…(Holmbom et al, 2003). Best known among those from the genus Abiesis secoisolariciresinol, a potent natural antioxidant found in balsam knots alongside lariciresinol which has proven bioactivity against breast cancer (Saarinen et al, 2008). Knot extracts contain juvabione and sesquiterpenoïd acids as well (Figure 1).…”