Inhibition by 1'-acetoxychavicol acetate of lipopolysaccharide- and interferon-gamma-induced nitric oxide production through suppression of inducible nitric oxide synthase gene expression in RAW264 cells

Ohata, Takeji; Fukuda, Kazunori; Murakami, Akira; Ohigashi, Hajime; Sügimura, Takashi; Wakabayashi, Keiji

doi:10.1093/carcin/19.6.1007

Cited by 43 publications

(23 citation statements)

References 42 publications

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“…The down-regulation of COX-2 by ACA is consistent with a previous report that showed suppression of COX-2 expression induced by LPS/IFN-␥ in mouse macrophages (69). Our results may also explain the down-regulation of inducible NO synthase expression (14), which is also regulated by NF-B.…”

Section: Discussionsupporting

confidence: 93%

“…Protein tyrosine phosphorylation and reduction of cellular sulfhydryl groups have been implicated in ACA-induced apoptosis (12). Still other reports have indicated that ACA has antioxidant and anti-inflammatory activities (13,14), inhibits xanthine oxidase (4), and suppresses inducible NO synthase gene expression (14). How ACA mediates antitumor activities is not well understood.…”

Section: Identification Of a Novel Blocker Of Ib␣ Kinase That Enhancementioning

confidence: 99%

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Identification of a Novel Blocker of IκBα Kinase That Enhances Cellular Apoptosis and Inhibits Cellular Invasion through Suppression of NF-κB-Regulated Gene Products

Ichikawa

Takada

Murakami

et al. 2005

The Journal of Immunology

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1′-Acetoxychavicol acetate (ACA), extracted from rhizomes of the commonly used ethno-medicinal plant Languas galanga, has been found to suppress chemical- and virus-induced tumor initiation and promotion through a poorly understood mechanism. Because several genes that regulate cellular proliferation, carcinogenesis, metastasis, and survival are regulated by activation of the transcription factor NF-κB, we postulated that ACA might mediate its activity through modulation of NF-κB activation. For this report, we investigated the effect of ACA on NF-κB and NF-κB-regulated gene expression activated by various carcinogens. We found that ACA suppressed NF-κB activation induced by a wide variety of inflammatory and carcinogenic agents, including TNF, IL-1β, PMA, LPS, H2O2, doxorubicin, and cigarette smoke condensate. Suppression was not cell type specific, because both inducible and constitutive NF-κB activations were blocked by ACA. ACA did not interfere with the binding of NF-κB to the DNA, but, rather, inhibited IκBα kinase activation, IκBα phosphorylation, IκBα degradation, p65 phosphorylation, and subsequent p65 nuclear translocation. ACA also inhibited NF-κB-dependent reporter gene expression activated by TNF, TNFR1, TNFR-associated death domain protein, TNFR-associated factor-2, and IκBα kinase, but not that activated by p65. Consequently, ACA suppressed the expression of TNF-induced NF-κB-regulated proliferative (e.g., cyclin D1 and c-Myc), antiapoptotic (survivin, inhibitor of apoptosis protein-1 (IAP1), IAP2, X-chromosome-linked IAP, Bcl-2, Bcl-xL, Bfl-1/A1, and FLIP), and metastatic (cyclooxygenase-2, ICAM-1, vascular endothelial growth factor, and matrix metalloprotease-9) gene products. ACA also enhanced the apoptosis induced by TNF and chemotherapeutic agents and suppressed invasion. Overall, our results indicate that ACA inhibits activation of NF-κB and NF-κB-regulated gene expression, which may explain the ability of ACA to enhance apoptosis and inhibit invasion.

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Section: Discussionsupporting

confidence: 93%

Section: Identification Of a Novel Blocker Of Ib␣ Kinase That Enhancementioning

confidence: 99%

Identification of a Novel Blocker of IκBα Kinase That Enhances Cellular Apoptosis and Inhibits Cellular Invasion through Suppression of NF-κB-Regulated Gene Products

Ichikawa

Takada

Murakami

et al. 2005

The Journal of Immunology

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“…One such nonsteroidal anti-inflammatory drug is ibuprofen, which reduces iNOS activity in rat alveolar macrophage cultures stimulated by lipopolysaccharide and IFN-␥ (44). Some natural products including resveratrol (45), carnosol (46), and 1Ј-acetoxychavicol acetate (47), have been shown to inhibit iNOS gene expression and to reduce its activity. The mechanism(s) for their ability to elicit dual inhibitory effects have not been determined; however, the influence of these natural products on iNOS gene expression may be due, at least in part, to inhibition of nuclear factor B activation (48).…”

Section: Discussionmentioning

confidence: 99%

Chemopreventive Effects of a Selective Nitric Oxide Synthase Inhibitor on Carcinogen-Induced Rat Esophageal Tumorigenesis

et al. 2004

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The inducible nitric oxide synthase (iNOS) generates a high concentration of nitric oxide (NO) in tissues. Increased NO production is associated with many disorders including esophageal cancer. Previous studies in our laboratory demonstrated an association between increased iNOS expression and the development of N-nitrosomethylbenzylamine (NMBA)-induced tumors in the rat esophagus. On the basis of these observations, we initiated a bioassay to evaluate the ability of S,S-1,4-phenylene-bis(1,2-ethanediyl)bis-isothiourea (PBIT), a selective iNOS inhibitor, to prevent the progression of esophageal tumors in rats preinitiated with NMBA. Rats were given s.c. injections of NMBA (0.25 mg/kg body weight) three times per week for 5 weeks. One week later, they were fed a synthetic diet containing either 50 or 100 ppm PBIT until the end of the bioassay (25 weeks). PBIT reduced the incidence of esophageal cancer from 96% in NMBA-treated rats to 83% and 77% (P < 0.05) in rats treated with 50 and 100 ppm PBIT, respectively. Tumor multiplicity was reduced from 3.64 ؎ 0.42 tumors per esophagus in NMBA-treated rats to 1.79 ؎ 0.25 (P < 0.001) and 1.50 ؎ 0.24 (P < 0.0001) in rats treated with 50 and 100 ppm PBIT, respectively. PBIT reduced the production of NO in NMBAinduced preneoplastic and papillomatous esophageal lesions when compared with comparable lesions in rats treated with NMBA only. iNOS mRNA expression was not modulated by PBIT. These observations suggest that iNOS plays a role in tumor development and that its selective inhibitor, PBIT, significantly inhibits esophageal tumor progression presumably through reducing the production of NO.

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“…DISCUSSION ACA has been found to be a potential inhibitor of tumorpromotion in an in vitro Epstein-Barr virus activation test Re-80 1 18 10 (55.6) 2.0 ± 3.1 6.8 ± 18.0 * 12 (66.7) 1.7 ± 1.9 4.2 ± 11.7 15 (83.3) 3.7 ± 3.9 5.5 ± 15.4 Re-80 0.4 18 6 (33.3) 0.9 ± 1.9 2.3 ± 3.4 * 9 (50.0) 1.6 ± 3.3 8.7 ± 18.5 12 (66.7) 2.4 ± 4.0 6.4 ± 15.1 Am-580 20 18 3 (16.7) 0.2 ± 0.4 0.2 ± 0.1 15 (83.3) 3.1 ± 2.6 9.9 ± 5.3 15 (83.3) 3.3 ± 2.8 4.4 ± 5.2 Am-580 5 18 8 (44.4) 0.7 ± 1.0 0.4 ± 0.4 15 (83.3) 3.3 ± 3.1 5.5 ± 5.3 16 (88.9) 4.1 ± 3.8 4.6 ± 8.5 Am-55P 20 18 7 (38.9) 1.2 ± 2.6 6.9 ± 17.1 8 (44.4) 2.2 ± 3.6 2.2 ± 7.7 12 (66.7) 3.4 ± 4.8 3.8 ± 10.8 ACA 100 18 12 (66.7) 1.9 ± 2.6 0.7 ± 0.8 10 (55.6) 1.4 ± 1.9 6.1 ± 11.5 16 (88.9) 3.3 ± 3.0 2.9 ± 8.3 All-trans-retinoic acid 10 17 10 (58.8) 1.4 ± 2.1 0.5 ± 0.9 10 (58.8) 1.1 ± 1.4 3.1 ± 7.5 14 (82.4) 2.5 ± 2.6 1. for screening of edible plants from Thailand (Kondo et al, 1993;Murakami et al, 1995), and ACA showed chemopreventive or anti-tumor promotion activities in vivo studies in rats or mice treated with chemical carcinogens (Tanaka and Mori, 1995;Murakami et al, 1996;Ohnishi et al, 1996;Nakamura et al, 1998;Tanaka et al, 1997aTanaka et al, , 1997b. ACA inhibits xanthine oxidase activity and nitric oxide production (Noro et al, 1988;Ohata et al, 1998) involved in tumorigenesis (Pence and Reiners, 1987;Cerutti, 1994 chromosomal change, and activation of cytoplasmic signal transduction pathways related to cell growth (Cerutti, 1994). For this reason, it is to be expected that ACA would inhibit all stages of tumor development including initiation, promotion and progression.…”

Section: Incidences and Multiplicities Of Tumors In Different Organs mentioning

confidence: 99%

“…It has been shown to inhibit the activity of xanthine oxidases, including a nitric oxide (NO) synthase (Noro et al, 1998;Ohata et al, 1998). Reactive oxygen species are known to participate in all stages of carcinogenesis including initiation, promotion, and progression (Pence and Reiners, 1987;Cerutti, 1994), and therefore, xanthine oxidase inhibitors are expected to be chemopreventors.…”

Section: Introductionmentioning

confidence: 99%

Modifying Effects of 1'-Acetoxychavicol Acetate (ACA) and the Novel Synthetic Retinoids Re-80, Am-580 and Am-55P in a Two-Stage Carcinogenesis Model in Female Rats

et al. 2004

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Effects of dietary administration of 1 -acetoxychavicol acetate (ACA) and the novel synthetic retinoids 4- [1-hydroxy-3-oxo-3-(5,6,7,8-tetrahydro-3-hydroxy-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid (Re-80); 4- [(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carboxamido]benzoic acid (Am-580); and 6-[(3,5-di-tert-butylphenyl) carbamoyl]nicotinic acid (Am-55P) were examined using a two-stage rat carcinogenesis model. A total of 190 female SD rats was treated sequentially with 1,2-dimethylhydrazine (DMH, s.c.); 7,12-dimethylbenz(a)anthracene (DMBA, i.g.); and 2,2 -dihydroxy-di-n-propylnitrosamine (DHPN, in the drinking water) during the first three weeks (DDD-initiation), and an additional 60 rats received the vehicle alone (non-initiation). One week after the completion of the initiation period, they were divided into nine groups and administrated Re-80 (at dose levels of 1.0 or 0.4 ppm), Am-580 (20 or 4 ppm), Am-55P (20 ppm), ACA (100 ppm), all-trans-retinoic acid (10 or 2 ppm) or no supplement in the diet for 33 weeks, until survivors were euthanatized at week 37 weeks. After DDD-initiation, all-trans-retinoic acid at the high dose delayed the development of mammary tumors. The multiplicity of colon tumors in the group fed Am-55P and the incidences of nephroblastomas with ACA or Am-580 were decreased as compared with the control values, but the other chemicals had no modifying effects on tumor development in any organs. Thus, among ACA and the novel synthetic retinoids tested, only Am-55P showed a weak inhibitory effect on a neoplasm of general interest under the present experimental conditions.

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Inhibition by 1'-acetoxychavicol acetate of lipopolysaccharide- and interferon-gamma-induced nitric oxide production through suppression of inducible nitric oxide synthase gene expression in RAW264 cells

Cited by 43 publications

References 42 publications

Identification of a Novel Blocker of IκBα Kinase That Enhances Cellular Apoptosis and Inhibits Cellular Invasion through Suppression of NF-κB-Regulated Gene Products

Identification of a Novel Blocker of IκBα Kinase That Enhances Cellular Apoptosis and Inhibits Cellular Invasion through Suppression of NF-κB-Regulated Gene Products

Chemopreventive Effects of a Selective Nitric Oxide Synthase Inhibitor on Carcinogen-Induced Rat Esophageal Tumorigenesis

Modifying Effects of 1'-Acetoxychavicol Acetate (ACA) and the Novel Synthetic Retinoids Re-80, Am-580 and Am-55P in a Two-Stage Carcinogenesis Model in Female Rats

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