Xanthorrhizol inhibits 12-O-tetradecanoylphorbol-13-acetate-induced acute inflammation and two-stage mouse skin carcinogenesis by blocking the expression of ornithine decarboxylase, cyclooxygenase-2 and inducible nitric oxide synthase through mitogen-activated protein kinases and/or the nuclear factor- B

Chung, Won Yoon; Park, Jae Hee; Kim, Mi Jeong; Kim, Heui Ok; Hwang, Jae Kwan; Lee, Sang Kook; Park, Kwang Kyun

doi:10.1093/carcin/bgm005

Cited by 96 publications

(91 citation statements)

References 40 publications

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“…Because both c-Jun and JunB that play opposite roles in proliferation (41-43, 61) were increased in the KO mouse, overexpression of JunB could also counteract the proliferative effects of c-Jun. Furthermore, ERK and Akt have been identified as important regulators of NF-B activation in the skin (48,62,63), and consistent with this, we found that p65 phosphorylation was increased in the TR KO mice.…”

Section: Discussionsupporting

confidence: 88%

The Thyroid Hormone Receptors as Modulators of Skin Proliferation and Inflammation

Contreras‐Jurado

García-Serrano

Gómez-Ferrerı́a

et al. 2011

Journal of Biological Chemistry

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The actions of thyroid hormones are mediated by binding to nuclear receptors, TR␣ 4 and TR␤, that act as ligand-dependent transcription factors by association, generally as heterodimers with retinoid X receptors, with thyroid hormone response elements located in regulatory regions of target genes (1). TRs can also modulate expression of genes that do not contain a hormone response element by modulating the activity of other transcription factors and signaling pathways (2), including activator protein-1 (AP-1)-, cyclic AMP-response element-, and nuclear factor-B (NF-B)-dependent pathways (3-7).Studies with knock-out (KO) mice for TRs obtained by homologous recombination have indicated that KO mice for ␣1 and ␤ TR isoforms have different phenotypes (8 -10) and that the double KO mice, surprisingly, survive (11), indicating that these receptors are not required for viability. Although these animals show extreme resistance to thyroid hormones, they exhibit a milder phenotype than hypothyroid mice, indicating divergent consequences for hormone versus receptor deficiency for some actions.Although the skin is a target tissue for thyroid hormone action, no studies on the skin phenotype in TR KO mice have been reported. TR␣ and TR␤ mRNAs are present in the skin (12-15), and these receptors can regulate either positively or negatively the expression of selected keratins in cultured cells (16 -19). Clinical evidence (19 -27) as well as studies in hypothyroid mice and rats (28 -30) also suggest that thyroid hormones could be involved in epidermal proliferation and differentiation, hair growth, and wound healing besides affecting the function of dermal fibroblasts. A question emerging from these studies is how to distinguish between effects due to altered thyroid hormone levels and effects due to expression of specific TR isoforms.The TR KO mice represent an excellent model for the analysis of the role of these receptors in the skin and its response to hyperproliferative stimuli. Topical application of 12-O-tetradecanolyphorbol-13-acetate (TPA) to mouse skin is a well known model for induction of skin hyperproliferation and also promotes a strong inflammatory reaction that activates multiple immunostimulatory pathways. The skin response to TPA is associated with activation of several intracellular pathways (e.g. mitogen-activated protein kinases (MAPKs), AKT, NF-B, STAT3, and AP-1) as well as an increase in the content of chemical mediators, such as cytokines, chemokines, vasoactive peptides, prostaglandins, leukotrienes, and nitric oxide among others (31)(32)(33)(34).In this work, we have investigated skin proliferation and inflammation, before and after TPA application, in mice lacking TR␣1, TR␤, or both genes, comparing these responses with those of hypothyroid animals to distinguish the specific contributions of receptor expression and activation. We found that TRs and thyroid hormones are required for skin homeostasis after TPA treatment and that both receptor genes contribute to

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Section: Discussionsupporting

confidence: 88%

The Thyroid Hormone Receptors as Modulators of Skin Proliferation and Inflammation

Contreras‐Jurado

García-Serrano

Gómez-Ferrerı́a

et al. 2011

Journal of Biological Chemistry

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“…In our previous studies on carcinogenesis, xanthorrhizol suppressed cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in lipopolysaccharide (LPS)-induced RAW 264.7 cells and exhibited antimetastasis activity in a mouse spontaneous lung metastasis model (9,10). Recently, we also reported cancer chemopreventive activity mediated by xanthorrhizol and a plausible mechanism of action in a mouse two-stage carcinogenesis model (11). However, the underlying mechanisms of action through which xanthorrhizol inhibits cancer cell growth are yet not fully clarified.…”

Section: Introductionmentioning

confidence: 99%

Xanthorrhizol, a Natural Sesquiterpenoid, Induces Apoptosis and Growth Arrest in HCT116 Human Colon Cancer Cells

Kang¹,

Park

Chung

et al. 2009

J Pharmacol Sci

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Abstract. Xanthorrhizol is a sesquiterpenoid from the rhizome of Curcuma xanthorrhiza. In our previous studies, xanthorrhizol suppressed cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, inhibited cancer cell growth, and exerted an anti-metastatic effect in an animal model. However, the exact mechanisms for its inhibitory effects against cancer cell growth have not yet been fully elucidated. In the present study, we investigated the growth inhibitory effect of xanthorrhizol on cancer cells. Xanthorrhizol dose-dependently exerted antiproliferative effects against HCT116 human colon cancer cells. Xanthorrhizol also arrested cell cycle progression in the G0/G1 and G2/M phase and induced the increase of sub-G1 peaks. Cell cycle arrest was highly correlated with the downregulation of cyclin A, cyclin B1, and cyclin D1; cyclin-dependent kinase 1 (CDK1), CDK2, and CDK4; proliferating cell nuclear antigen; and inductions of p21 and p27, cyclin-dependent kinase inhibitors. The apoptosis by xanthorrhizol was markedly evidenced by induction of DNA fragmentation, release of cytochrome c, activation of caspases, and cleavage of poly-(ADP-ribose) polymerase. In addition, xanthorrhizol increased the expression and promoter activity of pro-apoptotic non-steroidal antiinflammatory drug-activated gene-1 (NAG-1). These findings provide one plausible mechanism for the growth inhibitory activity of xanthorrhizol against cancer cells.

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“…Inflammatory leukocytes, such as macrophages when activated by many stimuli, result in the induction of pro-inflammatory protein and enzymes including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) [7]. Consequently, suppressing the induction of COX-2 and iNOS is a key strategy for cancer chemoprevention in various human organs [8].…”

Section: Introductionmentioning

confidence: 99%

Some Phytochemicals and Anti-inflammation Effect of Juice from <i>Tiliacora triandra</i> Leaves

Weerawatanakorn¹,

Rojsuntornkitti²,

Pan³

et al. 2018

JFNR

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Tiliacora triandra (TT), native to Southeast Asia, has been widely used as folk medicine and in cuisines in many areas. Although little scientific evidence supports the health benefits of TT leaves, the juice extracted from TT leaves has become popular for consumers among all socioeconomic classes. Thus, this study aims to evaluate the phytochemical profile and anti-inflammatory properties of juice extracted from TT leaves. The result revealed that, the highest total phenolic contents (199.92 mg GAE/g), total flavonoid contents (29.76 mg RUE/g), and extraction yield (61.2%) of the lyophilized TT leaves juice powder were found in the solvent mixture of ethanol, water, and acetone extracts. The highest DPPH radical scavenging value (90.95%) of the lyophilized TT leaves juice powder was found in hot water extract. By HPLC analysis, total phenolic compounds of the lyophilized TT leaves juice powder was 3,938.1 mg/kg. Tannic acid, gallic acid, and rutin are the major phenolic compound and the juice is a rich source of chlorophyll compound (3,551.6 mg/kg). The lyophilized TT leaves juice down-regulated the induction of inflammatory iNOS and COX-2 proteins in LPS-stimulated macrophages. The results suggest that intake of TT leaves juice, providing various phenolic and chlorophyll compounds, has great potential for reducing the inflammatory process.

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Cited by 96 publications

References 40 publications

The Thyroid Hormone Receptors as Modulators of Skin Proliferation and Inflammation

The Thyroid Hormone Receptors as Modulators of Skin Proliferation and Inflammation

Xanthorrhizol, a Natural Sesquiterpenoid, Induces Apoptosis and Growth Arrest in HCT116 Human Colon Cancer Cells

Some Phytochemicals and Anti-inflammation Effect of Juice from <i>Tiliacora triandra</i> Leaves

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