Location: Natural Products Utilization Research
Title: Anti-Inflammatory Action of Pterostilbene is Mediated Through the p38 Mitogen-Activated Protein Kinase Pathway in Colon Cancer Cells Authors
|Paul, Shiby - RUTGERS UNIVERSITY|
|Lee, Hong Jin - RUTGERS UNIVERSITY|
|Ji, Yan - RUTGERS UNIVERSITY|
|Reddy, Bandaru - RUTGERS UNIVERSITY|
|Suh, Nanjoo - RUTGERS UNIVERSITY|
Submitted to: Cancer Prevention Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: April 13, 2009
Publication Date: June 23, 2009
Citation: Paul, S., Rimando, A.M., Lee, H., Ji, Y., Reddy, B.S., Suh, N. 2009. Anti-Inflammatory Action of Pterostilbene is Mediated Through the p38 Mitogen-Activated Protein Kinase Pathway in Colon Cancer Cells. Cancer Prevention Research. 2(7):650-657. Interpretive Summary: Previously, we have shown that pterostilbene inhibited the expression of certain inflammatory genes in the colon. Here, we investigated the mechanism of anti-inflammatory action of pterostilbene using cultured colon cancer cells. Treating the cells with a combination of substances that cause inflammation induced inflammatory genes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). The induction of iNOS and COX-2 was significantly suppressed by treatment with pterostilbene. The effect of pterostilbene on multiple cell signaling pathways that lead to inflammation was investigated. Only one pathway (p38 MAP kinase) was significantly inhibited, indicating that this is the key pathway for eliciting the anti-inflammatory activity of pterostilbene in cultured colon cancer cells.
Technical Abstract: Oxidation and nitration/nitrosation stress and generation of pro-inflammatory cytokines are hallmarks of inflammation. Since chronic inflammation is implicated in several pathological conditions in humans, including cancers of the colon, we have been interested in identifying new anti-inflammatory compounds as useful chemopreventive agents against colon cancer. We previously showed that pterostilbene (trans-3,5-dimethoxy-4’-hydroxystilbene), a structural analogue of resveratrol, is present in blueberries and that pterostilbene inhibited expression of certain inflammatory genes in the colon and suppressed aberrant crypt foci formation in an azoxymethane-induced model of colon carcinogenesis in rats. Here, we investigated the mechanism of anti-inflammatory action of pterostilbene using cultured HT-29 colon cancer cells. Pterostilbene reduced cell proliferation, down-regulated the expression of c-myc and cyclin D1, and increased the level of cleaved PARP. Treating HT-29 colon cancer cells with the combination of tumor necrosis factor-a, interferon-g and bacterial endotoxin lipopolysaccharide (LPS), induced inflammatory genes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). The induction of iNOS and COX-2 mRNA and protein was significantly suppressed by treatment with pterostilbene. To identify upstream signaling pathways that may contribute to the anti-inflammatory activity of pterostilbene, we investigated the effect of pterostilbene on multiple signaling pathways including NF-kB, JAK-STAT, ERK, p38, JNK, Akt, and PI-3-kinase. Only the p38 pathway was significantly inhibited by pterostilbene among the different mediators evaluated. Our data suggest that the p38 MAP kinase pathway is a key signal transduction pathway for eliciting the anti-inflammatory action of pterostilbene in cultured colon cancer cells.