Naturally occurring lignans efficiently induce apoptosis in colorectal tumor cells

Abstract

Plant-derived lignans caused cell loss by apoptosis in colorectal adenoma and carcinoma cells. Nordihydroguaiaretic acid (NDGA), commonly used for the inhibition of lipoxygenase isoenzymes, showed the strongest growth inhibition with an IC50 of 1.9+/-0.5 microg followed by epiashantin (IC50=9.8+/-4.5 microM) and arctigenin (IC50=16.5+/-8.5 microM). The lignans caused a time- and dose-dependent loss of mitochondrial membrane potential (MMP), down regulation of the anti-apoptotic protein bcl(xl) and an increase of the apoptotic index. The time interval until loss of MMP and down modulation of bcl(xl) became evident correlated with the efficiency of growth inhibition by NDGA, epiashantin and yangambin. Bcl2 and caspase 3 were not involved. NDGA also induced a shift of the culture population to the G2/M phase of the cell cycle. With respect to these results, naturally occurring lignans could be useful in the therapy and chemoprevention of colorectal tumors.

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

“…The molecular mechanism behind anticancer activity of lignans is not yet well characterized. Lignans have been reported to induce downregulation of the anti-apoptotic Bcl-2 proteins (Hausott et al, 2003) and to inhibit casein kinase II and protein kinase C a (Yokoyama et al, 2003). They can act as antioxidants protecting cells from oxidative stress (Kitts et al, 1999), or as inhibitors of steroid metabolizing Lignans sensitize prostate cancer cells to TRAIL E Peuhu et al enzymes (Adlercreutz et al, 1993).…”

Enhancing lignan biosynthesis by over‐expressing pinoresinol lariciresinol reductase in transgenic wheat

“…Epidemiological studies show an inverse association between dietary intake of lignans and the risk of cardiovascular disease [10,11]. Lignans also have potential protective roles against cancer in breast [12], prostate [13], and colon [14,15]. A study done in rats showed that exposure of 10% flaxseed (SDG-rich plant seeds) or the equivalent SDG levels during suckling suppressed chemical carcinogen 7, 12-dimethylbenz(α)anthracene (DMBA)-induced mammary tumorigenesis [16].…”

Induction of G1 arrest and apoptosis by schisandrin C isolated from Schizandra chinensis Baill in human leukemia U937 cells

“…Schisandrin C was obtained as colorless needles (from MeOH), C 22 at ‰ = 1.72 (1H, m) are indicative of the C-8 and C-7 methyl groups, respectively (Fig. 1B).…”

“…The seeds and fruits of S. chinensis are enriched in lignans, and more than 40 lignans have been isolated from this plant (15)(16)(17)(18)(19)(20)(21). Some lignans have previously been reported to induce cell cycle arrest and apoptosis in human cancer cell lines including leukemia cells (22)(23)(24)(25)(26). However, the underlying molecular mechanisms for their putative therapeutic effects are not clear.…”