Matairesinol

Inhibition of Akt signaling by the lignan matairesinol sensitizes prostate cancer cells to TRAIL-induced apoptosis.[Pubmed: 19935713]

Oncogene. 2010 Feb 11;29(6):898-908.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to be selectively pro-apoptotic in cancer cells, with minimal toxicity to normal tissues. Although this feature makes TRAIL a promising anticancer agent, not all cancer cell types are sensitive to TRAIL-induced apoptosis despite abundant expression of TRAIL receptors. Thus, combinatorial treatments to sensitize tumor cells to TRAIL-induced apoptosis have been in the focus of extensive research. Dietary lignans have shown cancer preventive and antitumorigenic activity, but the mechanisms behind these effects are poorly known.
METHODS AND RESULTS:
Here we observed that of the three tested lignan molecules, Matairesinol (MAT) was the most effective as a death receptor-sensitizing agent. MAT sensitized the androgen-dependent LNCaP cells to TRAIL-induced apoptosis both in the presence and absence of androgens. Treatment with MAT markedly decreased Akt activity, which has been implicated as a key signaling mechanism in the TRAIL resistance of LNCaP prostate cancer cells. The involvement of the pathway in the MAT-mediated sensitization was shown in rescue experiments using ectopic expression of constitutively active Akt.
CONCLUSIONS:
Owing to the high activity of phosphatidylinositol 3-kinase/Akt signaling in cancer, targeting this survival pathway with MAT could markedly benefit TRAIL-based tumor therapies, including those aimed at prostate cancer.

Radical and superoxide scavenging activities of matairesinol and oxidized matairesinol.[Pubmed: 16926506]

Biosci Biotechnol Biochem. 2006 Aug;70(8):1934-40.

The radical and superoxide scavenging activities of oxidized Matairesinols were examined.
METHODS AND RESULTS:
It could be assumed that the free benzylic position was important for higher radical scavenging activity. The different level of activity was observed between 7'-oxoMatairesinol (Mat 2) and 7-oxoMatairesinol (Mat 3). The activity of 8-hydroxyMatairesinol was lower than that of Matairesinol (Mat 1).
CONCLUSIONS:
The superoxide scavenging activity of the oxidized Matairesinols was also demonstrated for the first time. It is assumed that the pKa value of phenol in the oxidized Matairesinols affected this activity.

Matairesinol inhibits angiogenesis via suppression of mitochondrial reactive oxygen species.[Pubmed: 22483751]

Cytotoxicity of arctigenin and matairesinol against the T-cell lymphoma cell line CCRF-CEM.[Pubmed: 25922263]

J Pharm Pharmacol. 2015 Apr 29.

Arctigenin and Matairesinol possess a diversity of bioactivities. Here we investigated the cytotoxicity of arctigenin and Matairesinol against a T-cell lymphoma cell line CCRF-CEM and the underlying mechanisms that have not been explored before.
METHODS AND RESULTS:
The cytotoxic activity was investigated using MTT assay. The cell cycle arrest and reactive oxygen species (ROS) accumulation were determined by flow cytometric analysis. The apoptosis induction was assessed using Annexin V/Propidium Iodide assay. The gene quantification analysis was measured through real-time polymerase chain reaction.
CONCLUSIONS:
Arctigenin and Matairesinol exhibited significant antiproliferative activity against CCRF-CEM cells after 72 h treatment with IC50 values of 1.21 ± 0.15 μm and 4.27 ± 0.41 μm, respectively.

Biochem Biophys Res Commun. 2012 Apr 27;421(1):76-80.

Mitochondrial reactive oxygen species (mROS) are involved in cancer initiation and progression and function as signaling molecules in many aspects of hypoxia and growth factor-mediated signaling.
METHODS AND RESULTS:
Here we report that Matairesinol, a natural small molecule identified from the cell-based screening of 200 natural plants, suppresses mROS generation resulting in anti-angiogenic activity. A non-toxic concentration of Matairesinol inhibited the proliferation of human umbilical vein endothelial cells. The compound also suppressed in vitro angiogenesis of tube formation and chemoinvasion, as well as in vivo angiogenesis of the chorioallantoic membrane at non-toxic doses. Furthermore, Matairesinol decreased hypoxia-inducible factor-1α in hypoxic HeLa cells.
CONCLUSIONS:
These results demonstrate that Matairesinol could function as a novel angiogenesis inhibitor by suppressing mROS signaling.

Anti-osteoclastogenic activity of matairesinol via suppression of p38/ERK-NFATc1 signaling axis.[Pubmed: 24444335]

BMC Complement Altern Med. 2014 Jan 21;14:35.

Matairesinol is a plant lignan present in a wide variety of foodstuffs such as seeds, vegetables and fruits. It has various biological functions including anti-angiogenic, anti-cancer and anti-fungal activities, but its anti-osteoporotic activity, if any, is unknown.
METHODS AND RESULTS:
For osteoclast differentiation, primary mouse bone marrow-derived macrophage cells (BMMs) were cultured for 4 days in the presence of RANKL and M-CSF with the vehicle (DMSO) or Matairesinol. Cell cytotoxicity was examined by CCK-8 assay. Gene expression of NFATc1, TRAP, OSCAR, v-ATPasev0d2 were observed in the presence or absence of Matairesinol (10 μM) for the indicated times. For evaluating the involvement of NFATc1 in the anti-osteoclastogenic action of Matairesinol, BMMs were infected with pMX-IRES-GFP or pMX-IRES-CA-NFATc1-GFP for 8 h with polybrene, and then infected BMMs were cultured with M-CSF and RANKL for 4 days in the presence or absence of Matairesinol (10 μM). MAPK signaling activation was examined by immunoblotting. For measuring the resorptive activity of mature osteoclasts, osteoclasts and osteoblasts were co-cultured on BioCoat Osteologic MultiTest slides, and treated with Matairesinol for 24 h. Here we show that Matairesinol dose-dependently inhibited the RANKL-induced differentiation of BMMs into osteoclasts by downregulating RANKL-induced expression and activity of NFATc1. Ectopic overexpression of NFATc1 blunted the anti-osteoclastogenic effect of Matairesinol implicating NFATc1 in the action of Matairesinol. Additionally, Matairesinol blocked the RANKL-induced activation of p38 and ERK in BMMs, but had no effect on bone resorption activity in mature osteoclasts.
CONCLUSIONS:
Taken together, our results suggest that the anti-osteoporotic activity of Matairesinol could arise from its anti-osteoclastogenic potential via p38/ERK-NFATc1 signaling, but not by way of anti-resorptive action.