COX‐2 and iNOS, good targets for chemoprevention of colon cancer

Watanabe, Kouji; Kawamori, Toshihiko; Nakatsugi, Seiichi; Wakabayashi, Keiji

doi:10.1002/biof.5520120120

Cited by 91 publications

(67 citation statements)

References 17 publications

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“…The number of COX-2, NFkB and iNOS immunoreactive cells was signifi cantly higher after DMH application than in the control group [13]. All detected changes were also seen in others studies on DMHinduced carcinogenesis in rats, but also in carcinogenesis in humans and confi rm that activation of infl ammatory signaling pathways are infl uenced by DMH and are the evidence of the interaction of chronic infl ammation with carcinogenesis.…”

Section: Resultssupporting

confidence: 73%

Inulin Diet Intervention on Chemopreventive and Inflammatory Markers in Tumorigenesis of Colorectal Cancer

et al. 2014

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The aim of this experiment was to investigate the infl uence of inulin administration on chemopreventive and infl ammatory markers in dimethylhydrazine induced colorectal cancer development in rats. A group of 30 Sprague-Dawley rats was divided into a control group (CG), a group with dimethylhydrazine (DMH), and a group given dimethylhydrazine combined with the prebiotic (DMH+PRE). Dimethylhydrazine injection signifi cantly (p<0.001) elevated the immunoreactivity chemopreventive markers COX-2, NFκB, iNOS, elevated serum and jejunal mucosa levels of proinfl ammatory cytokine IL-2, and decreased serum and jejunal mucosa levels of regulatory cytokine IL-10. Inulin diet intervention signifi cantly suppressed immunoreactivity of COX-2, NFκB, iNOS positive cells in the tunica mucosae and tela submucosae of rat colon tissue, increased levels of IL-2 and decreased levels of IL-10. By determining the chemopreventive markers COX-2, iNOS and NFkB, which can be characterized as infl ammatory markers, we confi rmed the presence of infl ammation in the colon as the number of COX-2, NFkB and iNOS immunoreactive cells was signifi cantly higher after DMH application than in the control group. These fi ndings indicate that dietary intake of inulin suppressed the expression of the observed markers, which play an important role in carcinogenesis and infl ammation, which predispose the use of inulin in the prevention or treatment of human chronic diseases and its use as a nutritional supplement in veterinary medicine.

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Section: Resultssupporting

confidence: 73%

Inulin Diet Intervention on Chemopreventive and Inflammatory Markers in Tumorigenesis of Colorectal Cancer

et al. 2014

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“…The activation of transcriptional factors Nf-kB and AP-1 are known to be involved in the pathogenesis of numerous cancers (Fujioka et al, 2004). It is also known that overxpression of iNOS and COX2 by AP-1 and Nf-kB, respectively, is involved in the pathogenesis of colon cancer (Watanabe et al, 2000). These data clearly suggest that pectin inactivates several key oncogenic factors in cancer as shown in Fig.…”

Section: Pectin Mcp and Their Molecular Interaction In Cancermentioning

confidence: 69%

Plant Pectin: A Potential Source for Cancer Suppression

Niture¹

2013

American Journal of Pharmacology and Toxicology

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Pectin is a branched polysaccharide present widely in a variety of fruits. It has been of high interest to cancer biologists due to its involvement in metal/carcinogen detoxification and its anti-carcinogenic properties. In particular, Citrus Pectin (CP) and Modified Citrus Pectin (MCP) have been shown to have a significant inhibitory role in cancer cell metastasis, invasion, angiogenesis and survival. The interactions and inactivation of oncogenes by CP and MCP in prostate, breast, liver, lung, melanoma and multiple myeloma cancers suggest that CP and MCP could play an important role in cancer chemotherapy and chemoprevention. In this review, we focus on the biological function of pectin with respect to its properties, sources, structure and its potential role in carcinogen detoxification and cancer suppression.

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“…22,23) Chinese herbs including Sellaginella genus plants have been used as alternative anti-cancer agents in East Asia. 10,24) Hence, the present data provide a possible mechanistic basis for the anti-tumor or chemopreventive effect of Sellaginella extracts.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Nuclear Factor-.KAPPA.B Activation by 2',8"-Biapigenin

Woo

Pokharel

Yang

et al. 2006

Biological & Pharmaceutical Bulletin

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Chemoprevention is considered to be one of the most promising strategies for the prevention of human cancers. It is defined as the use of either natural or synthetic compounds to block or retard the carcinogenic process, and many natural candidates including epigallocatechin, genistein and sulforaphane have been evaluated in terms of malignancy prevention. 1-3)Recently, it was suggested that chronic inflammation is associated with carcinogenesis. 4,5) Chronic inflammation leads to the induction of specific enzymes in affected tissues and cells. In particular, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are responsible for the exaggerated production of NO and prostaglandins, respectively, and are believed to be involved in the pathogenesis of cancer.6,7) COX-2 expression increases during tumor progression in the stomach, suggesting that COX-2 participates in gastric tumorigenesis.8) It has also been reported that there is a strong positive relationship between the presence of iNOS and the frequency of mutation in colon tumor tissues. 9)Hence, the overproduction of prostaglandins and NO may act as both an endogenous initiator and as a promoter of carcinogenesis and specific inhibitors of COX-2 or iNOS might have applications as chemopreventive agents in human cancer. Lee et al. 10) reported that the water-extracted fraction of Selaginella tamariscina (Selaginellaceae) efficiently increased p53 gene expression and induced G1 arrest, suggesting that S. tamariscina is a candidate chemopreventive. Crude extracts of S. tamariscina also reduced the production of proinflammatory cytokines, interleukin-1b, and tumor necrosis factor-a in human mesangial cells.11) As a part of our program to screen for potential cancer chemopreventive compounds from medicinal plants, we isolated 2Ј,8Љ-biapigenin from S. tamariscina (Fig. 1). The biological activity of 2Ј,8Љ-biapigenin has not been studied.In the present study, we investigated the modulating effects of the bi-flavonoid, 2Ј,8Љ-biapigenin on the expressions and activities of iNOS and COX-2 induced by lipopolysaccharide (LPS) in Raw264.7 macrophage cells. We found that 2Ј,8Љ-biapigenin inhibited nuclear factor (NF)-kB activation, and that this action is required for its blocking effects on iNOS and COX-2. MATERIALS AND METHODS Extraction and Isolation of 2,8؆-Biapigenin WholeSelaginella tamariscina (600 g) was extracted with MeOH at room temperature to afford 50.5 g of residue. The methanol extract was suspended in water and then sequentially partitioned in dichloromethane, ethyl acetate, and n-butanol. Three grams of the EtOAc fraction was subjected to silica gel column chromatography using a CHCl 3 -MeOH-H 2 O (12 : 1 : 0.1→8 : 1 : 0.1→5 : 1 : 0.1→2 : 1 : 0.1→1 : 1 : 0.1→Me OH only) gradient elution system. Fractions were combined based on their TLC patterns to yield subfractions designated as E1-E10. Subfraction E4 (438.9 mg) was purified by Sephadex LH 20 column chromatography using MeOH : H 2 Oϭ2 : 1 as eluant to give four subfractions (E41-E44). ...

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COX‐2 and iNOS, good targets for chemoprevention of colon cancer

Cited by 91 publications

References 17 publications

Inulin Diet Intervention on Chemopreventive and Inflammatory Markers in Tumorigenesis of Colorectal Cancer

Inulin Diet Intervention on Chemopreventive and Inflammatory Markers in Tumorigenesis of Colorectal Cancer

Plant Pectin: A Potential Source for Cancer Suppression

Inhibition of Nuclear Factor-.KAPPA.B Activation by 2',8"-Biapigenin

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