Pharmacological profile of JTE-522, a novel prostaglandin H synthase-2 inhibitor, in rats

Matsushita, Mutsuyoshi; Masaki, Michiko; Yagi, Yuki; Tanaka, Takashi; Wakitani, Korekiyo

doi:10.1007/s000110050225

Cited by 48 publications

(36 citation statements)

References 27 publications

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“…Furthermore, we examined the effects of COX-2 specific inhibitors, NS-398 79 and JTE-522, 67 on growth of 4 BDC and 1 GBC cell lines in vitro. As described previously in other cancer cell lines, 29,80 these 2 COX-2 selective inhibitors inhibited the proliferation of BDC and GBC cell lines in dose-and time-dependent manner in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…Nonselective inhibitors showed suppressive effects only at very high concentration. JTE-522 has been reported to possess the selective inhibitory effects of COX-2, 67,81 and to inhibit colon cancer cell growth by inducing apoptosis or reducing the expression of MMPs. 80 These data do suggest that COX-2 protein does effect, at least in part, the proliferation program of BDC.…”

Section: Discussionmentioning

confidence: 99%

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Differential expression of cyclooxygenase-2 (COX-2) in human bile duct epithelial cells and bile duct neoplasm

et al. 2001

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Differential expression of cyclooxygenase-2 (COX-2) in human bile duct epithelial cells and bile duct neoplasm

et al. 2001

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“…Furthermore, recently developed selective COX-2 inhibitors such as celecoxib have been shown to suppress colon carcinogenesis in experimental animals 8 -10 and humans with less toxicity than nonselective NSAIDs. 11,12 Selective COX-2 inhibitors have emerged as a promising chemoprevention strategy for colorectal cancers.JTE-522, a novel selective inhibitor of rat and human COX-2, 13 has been shown to reduce the number and growth of adenomas in APC⌬-474 knockout mice. 14,15 This compound also inhibited liver and lung metastases of colon cancer expressing COX-2 but lacked effect on those lacking COX-2 expression in the nude mouse xenograft model.…”

mentioning

confidence: 99%

“…JTE-522, a novel selective inhibitor of rat and human COX-2, 13 has been shown to reduce the number and growth of adenomas in APC⌬-474 knockout mice. 14,15 This compound also inhibited liver and lung metastases of colon cancer expressing COX-2 but lacked effect on those lacking COX-2 expression in the nude mouse xenograft model.…”

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confidence: 99%

JTE‐522, a selective cyclooxygenase‐2 inhibitor, inhibits induction but not growth and invasion of 1,2‐dimethylhydrazine‐induced tubular adenocarcinomas of colon in rats

Wei

Morimura

Wanibuchi

et al. 2004

Intl Journal of Cancer

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We have previously demonstrated that JTE-522, a selective cyclooxygenase-2 (COX-2) inhibitor, inhibited development of aberrant crypt foci (ACF) in rats, a putative preneoplastic lesion in colon, and suggested its inhibitory potential in rat colon carcinogenesis. To evaluate the chemopreventive properties of JTE-522, the present study was design to evaluate the inhibitory effects of JTE-522 on rat colon tumorigenesis induced by 1,2-dimethylhydrazine (DMH). Rats at 6 weeks of age were divided into 4 groups. One week after the start of the experiment, all rats received DMH by s.c. injection at a dose of 40 mg/kg body weight once a week for 4 successive weeks. As the initiation and postinitiation treatment groups, groups 1-3 were fed diets containing 0, 50, or 150 ppm JTE-522, respectively, from the start of the study to the end. As the postinitiation treatment group, group 4 was given 150 ppm JTE-522 from 1 week after the last DMH injection to the end of the study. Forty weeks after the start of the experiment, administration of 150 ppm JTE-522 during both initiation and postinitiation stages significantly inhibited the incidences of tubular adenocarcinomas and total carcinomas, as well as total tumors in the colon. The inhibitory effect of JTE-522 was most prominent for tubular adenocarcinomas, but was not observed in the nontubular carcinomas (signet-ring cell and mucinous carcinomas). Almost equal inhibitory effects on tubular adenocarcinomas were also observed in the rats given 150 ppm JTE-522 during the postinitiation stage, suggesting that its major anticancer action is at the postinitiation phase. However, JTE-522 had no effect on the size or invasive extent of tubular adenocarcinomas. Furthermore, microarray analyses revealed that JTE-522 had no effect on gene expression levels in DMH-induced tubular adenocarcinomas. These findings suggest that JTE-522 possesses chemopreventive activity against induction but not progression of tubular adenocarcinomas in rat colon. In view of the significant inhibitory effects of JTE-522 on ACF, its major anticancer action may occur in the postinitiation stage but before the malignant conversion stage of DMH-induced colon carcinogenesis.Key words: JTE-522; selective cyclooxynenase-2 inhibitor; colon carcinogenesis; tubular adenocarcinoma; chemoprevention Colorectal cancer leads to approximately 550,000 annual deaths worldwide 1 and is therefore a major public health problem and underlines the need for effective chemopreventive strategies. The protective effect of traditional nonsteroidal antiinflammatory drugs (NSAIDs), such as aspirin and sulindac, for colon cancer has been well documented in epidemiologic and animal studies. 2 However, their use for chemoprevention of colon cancer has been hindered by their potential gastrointestinal and renal toxicity. It is now known that nonselective NSAIDs inhibit activities of cyclooxygenases (COX), and inhibition of COX-2 may well explain their chemopreventive effect, whereas inhibition of COX-1 is believed to be responsible for man...

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“…JTE-522, a selective COX-2 inhibitor, was provided by Japan Tobacco, Inc. (Tokyo, Japan). 29 PD098059, an MAPK kinase inhibitor, and AG1478, a selective EGF receptor inhibitor, were from Calbiochem (La Jolla, CA). At the indicated times, CDCA was dissolved in ethanol; JTE-522, PD98059 and AG1478 were dissolved in dimethyl sulfoxide.…”

Section: Antibodies and Reagentsmentioning

confidence: 99%

Chenodeoxycholic acid stimulates the progression of human esophageal cancer cells: A possible mechanism of angiogenesis in patients with esophageal cancer

Soma

Kaganoi

Kawabe

et al. 2006

Intl Journal of Cancer

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Bile acids are known to promote the growth of gastrointestinal cancer. However, the underlying mechanism remains unclear. We examined whether bile acids induce tumor growth via the cyclooxygenase (COX)-2 angiogenic pathway. In vitro, esophageal squamous cell carcinoma (ESCC) cells and esophageal adenocarcinoma cells were studied. Production of prostaglandin E2 (PGE2) and vascular endothelial growth factor (VEGF) in response to treatment with chenodeoxycholic acid (CDCA) was assessed by enzyme-linked immunosorbent assay (ELISA). COX-2 protein and VEGF protein were measured by immunoblot analysis, and COX-2 activity was measured by ELISA. In vivo, CDCA was administered to ESCC cell-bearing mice. Tumor tissues were analyzed immunohistochemically, and microvessel density was evaluated. Clinically, 134 patients with ESCC who underwent esophagectomy were studied. In vitro, CDCA induced the production of PGE2 and VEGF in dose-and time-dependent manners, and these effects were attenuated by a selective COX-2 inhibitor, mitogenactivated protein kinases inhibitor, or epidermal growth factor receptor inhibitor. CDCA-induced COX-2 in the cell lysate increased the secretion of VEGF into the culture medium. In vivo, CDCA markedly enhanced tumor growth and increased vascularization. Clinically, patients whose tumors expressed both COX-2 and VEGF had poor outcomes. Our results suggest that bile acids, important constituents of duodenal fluid, stimulate the development of human esophageal cancer by promoting angiogenesis via the COX-2 pathway. ' 2006 Wiley-Liss, Inc.

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Pharmacological profile of JTE-522, a novel prostaglandin H synthase-2 inhibitor, in rats

Cited by 48 publications

References 27 publications

Differential expression of cyclooxygenase-2 (COX-2) in human bile duct epithelial cells and bile duct neoplasm

Differential expression of cyclooxygenase-2 (COX-2) in human bile duct epithelial cells and bile duct neoplasm

JTE‐522, a selective cyclooxygenase‐2 inhibitor, inhibits induction but not growth and invasion of 1,2‐dimethylhydrazine‐induced tubular adenocarcinomas of colon in rats

Chenodeoxycholic acid stimulates the progression of human esophageal cancer cells: A possible mechanism of angiogenesis in patients with esophageal cancer

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