Arachidonic acid cascade inhibitors modulate phorbol ester-induced oxidative stress in female ICR mouse skin: differential roles of 5-lipoxygenase and cyclooxygenase-2 in leukocyte infiltration and activation

Nakamura, Yoshimasa; Kozuka, Mayumi; Naniwa, Kisa; Takabayashi, Satoko; Torikai, Koji; Hayashi, Ryohei; Satô, Tadashi; Ohigashi, Hajime; Osawa, Toshihiko

doi:10.1016/s0891-5849(03)00440-4

Cited by 43 publications

(29 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The 5-Lox and Cox2 pathways are activated together during inflammation, and blocking one pathway may activate the other (39,40). In a phorbol ester -induced mouse dermatitis model, 5-Lox was mainly involved in the priming event, whereas Cox2 was involved in subsequent oxidative stress (41). Our results clearly showed that 5-Lox and Cox2 were up-regulated at the early stages of oral carcinogenesis.…”

Section: Discussionmentioning

confidence: 53%

Overexpression of 5-Lipoxygenase and Cyclooxygenase 2 in Hamster and Human Oral Cancer and Chemopreventive Effects of Zileuton and Celecoxib

Sood

Wang

et al. 2005

Clinical Cancer Research

119

View full text Add to dashboard Cite

Purpose: Previous studies have suggested an important role of aberrant arachidonic acid metabolism, especially the cyclooxygenase (Cox) pathway, in oral carcinogenesis. However, it is unknown whether the 5-lipoxygenase (5-Lox) pathway contributes to oral carcinogenesis, and whether combination of inhibitors of both pathways may have synergistic or additive effects of chemoprevention.Experimental Design: 5-Lox expression was examined in 7,12-dimethylbenz[a]anthracene (DMBA) --induced hamster and human oral cancer tissues by immunohistochemistry, and Cox2 expression was investigated in hamster oral tissues using in situ hybridization. Zileuton (a specific 5-Lox inhibitor) and celecoxib (a specific Cox2 inhibitor), either alone or in combination, were investigated for their chemopreventive effects on the DMBA-induced hamster model at the post-initiation stage through topical application.Results: 5-Lox was overexpressed during oral carcinogenesis in hamsters and humans, as well as Cox2 in the hamster tissues. In a chemoprevention study using the postinitiation DMBA model, incidence of hamster oral squamous cell carcinoma was reduced from 76.9% (20 of 26) to 45.8% (11 of 24, P < 0.05) and 32.1% (9 of 28, P < 0.01) by 3% and 6% topical zileuton, respectively; and to 57.6% (15 of 26, P > 0.05) and 50% (12 of 24, P < 0.05) by 3% and 6% topical celecoxib, respectively. When used in combination, celecoxib and zileuton (3% of each) had an additive inhibitory effect on the incidence of squamous cell carcinoma (36%, 9 of 25, P < 0.01). Other pathologic variables and the levels of leukotriene B4 and prostaglandin E2 of the hamster tissues were reduced as well.Conclusions: The results clearly showed that both 5-Lox and Cox2 played important roles in oral carcinogenesis. Zileuton and celecoxib prevented oral carcinogenesis at the post-initiation stage through their inhibitory effects on arachidonic acid metabolism.

show abstract

Section: Discussionmentioning

confidence: 53%

Overexpression of 5-Lipoxygenase and Cyclooxygenase 2 in Hamster and Human Oral Cancer and Chemopreventive Effects of Zileuton and Celecoxib

Sood

Wang

et al. 2005

Clinical Cancer Research

119

View full text Add to dashboard Cite

show abstract

“…Previous studies have revealed that many chemical or dietary factors can function as potential cancer chemopreventive agents, reflecting the induction effects of these compounds on phase II detoxifying and antioxidant enzymes, including HO-1, NQO1, and glutathione-S-transferases (45,46). In addition, the tumor promoter TPA induces lipid peroxidation in ICR mouse skin (47), and TPA also induces ROS overproduction and neoplastic transformation in mouse skin JB6 cells (48). In this study, the inhibitory effect of reserpine on TPAstimulated neoplastic transformation in a mouse epidermal JB6 P+ cell line was investigated to understand the chemopreventive potential of reserpine against skin tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Reserpine Inhibit the JB6 P+ Cell Transformation Through Epigenetic Reactivation of Nrf2-Mediated Anti-oxidative Stress Pathway

Bao

Zhang

et al. 2016

AAPS J

View full text Add to dashboard Cite

Abstract. Nuclear factor erythroid-2 related factor 2 (Nrf2) is a crucial transcription factor that regulates the expression of defensive antioxidants and detoxification enzymes in cells. In a previous study, we showed that expression of the Nrf2 gene is regulated by an epigenetic modification. Rauvolfia verticillata, a traditional Chinese herbal medicine widely used in China, possesses anticancer and antioxidant effects. In this study, we investigated how Nrf2 is epigenetically regulated by reserpine, the main active component in R. verticillata, in mouse skin epidermal JB6 P+ cells. Reserpine induced ARE (antioxidant response element)-luciferase activity in HepG2-C8 cells. Accordingly, in JB6 P+ cells, it upregulated the mRNA and protein levels of Nrf2 and its downstream target genes heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1), while it only increased the protein level of UDP-glucuronosyltransferase 1A1 (UGT1A1). Furthermore, reserpine decreased the TPA (12-O-tetradecanoylphorbol-13-acetate)-induced colony formation of JB6 cells in a dosedependent manner. DNA sequencing and methylated DNA immunoprecipitation further demonstrated the demethylation effect of reserpine on the first 15 CpGs of the Nrf2 promoter in JB6 P+ cells. Reserpine also reduced the mRNA and protein expression of DNMT1 (DNA methyltransferase 1), DNMT3a (DNA methyltransferases 3a), and DNMT3b (DNA methyltransferases 3b). Moreover, reserpine induced Nrf2 expression via an epigenetic pathway in skin epidermal JB6 P+ cells, enhancing the protective antioxidant activity and decreasing TPA-induced cell transformation. These results suggest that reserpine exhibits a cancer preventive effect by reactivating Nrf2 and inducing the expression of target genes involved in cellular protection, potentially providing new insight into the chemoprevention of skin cancer using reserpine.

show abstract

“…AA is a substrate for COX-2 and the induction of COX-2 activity can increase the generation of ROS, leading to damage to lipids, proteins, and DNA [38]. Of the AA-metabolizing enzymes, COX, which leads to the formation of PGs such as PGE 2 , PGF 2␣ , and PGD 2 , also plays a major role in inflammation and cell proliferation [39]. PGE 2 is the most abundant PG produced by microvascular endothelial cultures [40].…”

Section: Discussionmentioning

confidence: 99%

The effect of celecoxib, a selective COX-2 inhibitor, on liver ischemia/reperfusion-induced oxidative stress in rats

Öztürk

Gezici

Öztürk

2006

Hepatology Research

View full text Add to dashboard Cite

Arachidonic acid cascade inhibitors modulate phorbol ester-induced oxidative stress in female ICR mouse skin: differential roles of 5-lipoxygenase and cyclooxygenase-2 in leukocyte infiltration and activation

Cited by 43 publications

References 41 publications

Overexpression of 5-Lipoxygenase and Cyclooxygenase 2 in Hamster and Human Oral Cancer and Chemopreventive Effects of Zileuton and Celecoxib

Overexpression of 5-Lipoxygenase and Cyclooxygenase 2 in Hamster and Human Oral Cancer and Chemopreventive Effects of Zileuton and Celecoxib

Reserpine Inhibit the JB6 P+ Cell Transformation Through Epigenetic Reactivation of Nrf2-Mediated Anti-oxidative Stress Pathway

The effect of celecoxib, a selective COX-2 inhibitor, on liver ischemia/reperfusion-induced oxidative stress in rats

Contact Info

Product

Resources

About