secoisolariciresinol-diglucoside and Adenocarcinoma

Our previous study demonstrated that lignan metabolites enterolactone and enterodiol inhibited colonic cancer cell growth by inducing cell cycle arrest and apoptosis. However, the dietary lignans are naturally present as glycoside precursors, such as secoisolariciresinol diglucoside (SDG), which have not been evaluated yet. This study tested the hypothesis that dietary SDG might have a different effect than its metabolites in human colonic SW480 cancer cells. Treatment with SDG at 0 to 40 μmol/L for up to 48 hours resulted in a dose- and time-dependent decrease in cell numbers, which was comparable to enterolactone. The inhibition of cell growth by SDG did not appear to be mediated by cytotoxicity, but by a cytostatic mechanism associated with an increase of cyclin A expression. Furthermore, high-performance liquid chromatography analysis indicated that SDG in the media was much more stable than enterolactone (95% of SDG survival vs 57% of enterolactone after 48-hour treatment). When the cells were treated with either enterolactone or SDG at 40 μmol/L for 48 hours, the intracellular levels of enterolactone, as measured by high-performance liquid chromatography-mass spectrometry/electron spray ionization, were about 8.3 × 10(-8) nmol per cell; but intracellular SDG or potential metabolites were undetectable. Taken together, SDG demonstrated similar effects on cell growth, cytotoxicity, and cell cycle arrest when compared with its metabolite enterolactone. However, the reliable stability and undetectable intracellular SDG in treated cells may suggest that metabolism of SDG, if exposed directly to the colonic cells, could be different from the known degradation by microorganisms in human gut.

Topics: 4-Butyrolactone; Adenocarcinoma; Anticarcinogenic Agents; Butylene Glycols; Cell Cycle; Cell Line, Tumor; Chromatography, High Pressure Liquid; Colonic Neoplasms; Cyclin A; Cytostatic Agents; Dietary Carbohydrates; Dose-Response Relationship, Drug; Glucosides; Glycosides; Humans; Lignans; Mass Spectrometry

Dietary supplementation with flaxseed or its lignan secoisolariciresinol diglycoside (SDG) has reduced dimethylbenz[a]anthracene-induced mammary tumor size and number in rats. The objective of this study was to determine whether flaxseed has a dose-dependent effect on N-methyl-N-nitrosourea (MNU)-induced mammary tumor promotion and whether this effect can be attributed to its SDG. Two days after injection with MNU (50 mg/kg body wt i.p.), female Sprague-Dawley rats were fed a high-fat (20% soybean oil) AIN-93G basal diet alone (BD) or supplemented with flaxseed (2.5% F and 5% F) or SDG by gavage [SDG in 2.5% F (LSDG) and SDG in 5% F (HSDG)] for 22 weeks. Although tumors tended to be smallest in the 5% F group throughout the experimental period, flaxseed feeding did not significantly affect tumor size, multiplicity, or incidence in comparison to BD. However, there was a dose-dependent effect of SDG on tumor multiplicity. Tumor multiplicity was lowest in the HSDG group and highest in the LSDG group throughout treatment (p < 0.05), indicating that HSDG inhibited, whereas LSDG promoted, MNU-induced mammary tumor development. Tumor invasiveness and grade were decreased in all treatment groups compared with the BD (p < 0.032). Thus, although flaxseed feeding had no significant effect on tumor growth indexes, flaxseed and SDG treatment, regardless of dose, appeared to delay the progression of MNU-induced mammary tumorigenesis. Disparities between this study and previous studies on flaxseed may be related to differences in experimental design, the use and dose of a different carcinogen, and protective effects by the alpha-linolenic acid present in the BD.

Topics: Adenocarcinoma; Animals; Butylene Glycols; Carcinogens; Diet; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Flax; Glucosides; Lignans; Mammary Neoplasms, Experimental; Methylnitrosourea; Phytotherapy; Random Allocation; Rats; Rats, Sprague-Dawley