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Articles by S Paul
Total Records ( 3 ) for S Paul
  S Paul , A. M Rimando , H. J Lee , Y Ji , B. S Reddy and N. Suh
 

Oxidative/nitrosative stress and generation of proinflammatory cytokines are hallmarks of inflammation. Because chronic inflammation is implicated in several pathologic conditions in humans, including cancers of the colon, anti-inflammatory compounds may be useful chemopreventive agents against colon cancer. Stilbenes, such as resveratrol, have diverse pharmacologic activities, which include anti-inflammation, cancer prevention, a cholesterol-lowering effect, enhanced insulin sensitivity, and increased life span. 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 inflammation-related genes in the colon and suppressed aberrant crypt foci formation in rats. Here, we examined molecular mechanisms of the action of pterostilbene in colon cancer. Pterostilbene reduced cell proliferation, down-regulated the expression of c-Myc and cyclin D1, and increased the level of cleaved poly(ADP-ribose) polymerase. A combination of cytokines (tumor necrosis factor-, IFN-, and bacterial endotoxin lipopolysaccharide) induced inflammation-related genes such as inducible nitric oxide synthase and cyclooxygenase-2, which was significantly suppressed by treatment with pterostilbene. We further identified upstream signaling pathways contributing to the anti-inflammatory activity of pterostilbene by investigating multiple signaling pathways, including nuclear factor-B, Janus-activated kinase-signal transducer and activator of transcription, extracellular signal-regulated kinase, p38, c-Jun NH2-terminal kinase, and phosphatidylinositol 3-kinase. Cytokine induction of the p38-activating transcription factor 2 pathway was markedly inhibited by pterostilbene among the different mediators of signaling evaluated. By silencing the expression of the p38 isoform, there was significant reduction in cytokine induction of inducible nitric oxide synthase and cyclooxygenase-2. Our data suggest that the p38 mitogen-activated protein kinase cascade is a key signal transduction pathway for eliciting the anti-inflammatory action of pterostilbene in cultured HT-29 colon cancer cells.

  S Paul , A. J DeCastro , H. J Lee , A. K Smolarek , J. Y So , B Simi , C. X Wang , R Zhou , A. M Rimando and N. Suh
 

Stilbenes are phytochemicals present in grapes, berries, peanuts and red wine. A widely studied stilbene, resveratrol (trans-3,5,4'-trihydroxystilbene), has been shown to exert antioxidant, anti-inflammatory, chemopreventive and antiaging effects in a number of biological systems. We reported earlier that pterostilbene (trans-3,5-dimethoxy-4'-hydroxystilbene), a structurally related stilbene found in blueberries, was effective in reducing the incidence and multiplicity of aberrant crypt foci formation in the colon of rats injected with azoxymethane (AOM). Our present study was to identify the chemopreventive potential of pterostilbene with colonic tumor formation as an end point and further to evaluate the mechanistic action of pterostilbene during colon carcinogenesis. F344 rats were given two AOM injections subcutaneously when they were 7 and 8 weeks old and continuously fed the control or 40 p.p.m. pterostilbene diet for 45 weeks. Overall analyses indicated that pterostilbene reduced colon tumor multiplicity of non-invasive adenocarcinomas, lowered proliferating cell nuclear antigen and downregulated the expression of β-catenin and cyclin D1. Pterostilbene decreased mucosal levels of the proinflammatory cytokines, tumor necrosis factor-, interleukin (IL)-1β and IL-4. Colon tumors from pterostilbene-fed animals showed reduced expression of inflammatory markers as well as nuclear staining for phospho-p65, a key molecule in the nuclear factor-kappaB pathway. In HT-29 cells, pterostilbene reduced the protein levels of β-catenin, cyclin D1 and c-MYC, altered the cellular localization of β-catenin and inhibited the phosphorylation of p65. Our data with pterostilbene in suppressing colon tumorigenesis, cell proliferation as well as key inflammatory markers in vivo and in vitro suggest the potential use of pterostilbene for colon cancer prevention.

  H. J Lee , J Ju , S Paul , J. Y So , A DeCastro , A Smolarek , M. J Lee , C. S Yang , H. L Newmark and N. Suh
 

Purpose: Tocopherols are lipophilic antioxidants present in vegetable oils. Although the antioxidant and anticancer activities of -tocopherol (vitamin E) have been studied for decades, recent intervention studies with -tocopherol have been negative for protection from cancer in humans. The tocopherols consist of four isoforms, which are the , β, , and variants, and recent attention is being given to other isoforms. In the present study, we investigated the inhibitory effect of a tocopherol mixture rich in - and -tocopherols against mammary tumorigenesis.

Experimental Design: Female Sprague Dawley rats were treated with N-methyl-N-nitrosourea (NMU), and then fed diets containing 0.1%, 0.3%, or 0.5% mixed tocopherols rich in - and -tocopherols for 9 weeks. Tumor burden and multiplicity were determined, and the levels of markers of inflammation, proliferation, and apoptosis were evaluated in the serum and in mammary tumors. The regulation of nuclear receptor signaling by tocopherols was studied in mammary tumors and in breast cancer cells.

Results: Dietary administration of 0.1%, 0.3%, or 0.5% mixed tocopherols suppressed mammary tumor growth by 38%, 50%, or 80%, respectively. Tumor multiplicity was also significantly reduced in all three mixed tocopherol groups. Mixed tocopherols increased the expression of p21, p27, caspase-3, and peroxisome proliferator activated receptor-, and inhibited AKT and estrogen signaling in mammary tumors. Our mechanistic study found that - and -tocopherols, but not -tocopherol, activated peroxisome proliferator activated receptor- and antagonized estrogen action in breast cancer.

Conclusion: The results suggest that - and -tocopherols may be effective agents for the prevention of breast cancer.

 
 
 
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