Cyclooxygenase inhibitors in urinary bladder cancer:<i>in vitro</i>and<i>in vivo</i>effects

Mohammed, Sulma I.; Dhawan, Deepika; Abraham, Shaji; Snyder, Paul W.; Waters, David J.; Craig, Bruce A.; Lu, Ming; Wu, Lan; Zheng, Rong; Stewart, Janet; Knapp, Deborah W.

doi:10.1158/1535-7163.mct-05-0117

Cited by 53 publications

(45 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Therefore, we focused on a selective COX-2 inhibitor celecoxib used for the treatment of several diseases. It has also been reported that celecoxib inhibited the cell growth of high-grade bladder cancer in vitro and in vivo (5), and that celecoxib could induce apoptosis in various cancer cells independent of COX-2 inhibitory activity (6). However, the underlying mechanisms still remain unclear.…”

Section: Introductionmentioning

confidence: 99%

A Histone Deacetylase Inhibitor, OBP-801, and Celecoxib Synergistically Inhibit the Cell Growth with Apoptosis via a DR5-Dependent Pathway in Bladder Cancer Cells

Toriyama

Horinaka

Yasuda

et al. 2016

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

The prognosis of muscle-invasive bladder cancer with metastasis is poor. There have been no therapeutic improvements for many years, and an innovative therapy for muscle-invasive bladder cancer has been awaited to replace the conventional cytotoxic chemotherapy. Here, we show a candidate method for the treatment of bladder cancer. The combined treatment with a novel histone deacetylase (HDAC) inhibitor, OBP-801, and celecoxib synergistically inhibited cell growth and markedly induced apoptosis through the caspase-dependent pathway in high-grade bladder cancer cells. Furthermore, the combined treatment induced expression of death receptor 5 (DR5). We identified that knockdown of DR5 by small interfering RNA (siRNA) significantly suppressed apoptosis by the combined treatment. Therefore, we conjectured that the apoptosis induced by OBP-801 and celecoxib is at least partially dependent on DR5. However, it was interesting that the combined treatment drastically suppressed expression of DR5 ligand, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). These data suggest that there is no involvement of TRAIL in the induction of apoptosis by the combination, regardless of the dependence of DR5. Moreover, xenograft studies using human bladder cancer cells showed that the combined therapy suppressed tumor growth by upregulating expressions of DR5 and Bim. The inhibition of tumor growth was significantly more potent than that of each agent alone, without significant weight loss. This combination therapy provided a greater benefit than monotherapy in vitro and in vivo. These data show that the combination therapy with OBP-801 and celecoxib is a potential novel therapeutic strategy for patients with muscle-invasive bladder cancer. Mol Cancer Ther; 15(9); 2066-75. Ó2016 AACR.

show abstract

Section: Introductionmentioning

confidence: 99%

A Histone Deacetylase Inhibitor, OBP-801, and Celecoxib Synergistically Inhibit the Cell Growth with Apoptosis via a DR5-Dependent Pathway in Bladder Cancer Cells

Toriyama

Horinaka

Yasuda

et al. 2016

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

show abstract

“…14 Prostaglandins, produced by COX-2 activity, increase cell proliferation; inhibit apoptosis; promote angiogenesis; alter cellular adhesion, which allows for metastasis; inhibit immune surveillance; and may activate xenobiotics to reactive substances that are carcinogenic. 16 In human patients, recent studies found that COX-2 is upregulated in precancerous skin lesions, such as actinic keratosis and squamous-cell carcinoma (SCC). 3,12,19 In dogs, COX-2 was strongly expressed in neoplastic keratinocytes in all cases of SCC of the skin.…”

mentioning

confidence: 99%

Cyclooxygenase-2 Immunoreactivity in Equine Ocular Squamous-Cell Carcinoma

Rassnick

Njaa

2007

J VET Diagn Invest

View full text Add to dashboard Cite

Abstract. Squamous-cell carcinoma (SCC) is the second most common tumor in horses, and 40%-50% may occur in ocular and adnexal structures. Cyclooxygenase (COX)-2 is an inducible enzyme responsible for the production of prostaglandins that control cell growth and the development and progression of cancer. Mechanisms responsible for the initial upregulation of COX-2 in neoplasia are unclear; prolonged sunlight exposure and mutations in the p53 gene may be possibilities. Because the etiopathogenesis of ocular SCC in horses may involve ultraviolet sunlight and p53 mutations, the purpose of this study was to characterize the immunoreactivity of COX-2 in these tumors. Cyclooxygenase-2 expression was found in 6 of 22 (27%) paraffin-embedded equine SCCs. Cyclooxygenase-2 immunoreactivity was associated with the mitotic index (P , 0.001). Strategies to inhibit COX-2 by the use of topical or systemic COX-2 inhibitors might prove to be a safe and economical treatment in some horses with SCC.

show abstract

“…In addition, there is data indicating that the potentiation of gemcitabine effects seen in preclinical models of pancreatic cancer is mediated through modulation of other targets, such as nuclear factornB activation, which may contribute to the induction of apoptosis (43). There is evidence in models other than the pancreas that achieving efficacious drug concentrations is a problem with celecoxib and other COX inhibitors (44). To improve the bioavailability and decrease the systemic effects of celecoxib, alternative delivering strategies, such as chitosan-based, biodegradable slow-releasing platforms, (46).…”

Section: Discussionmentioning

confidence: 99%

Assessment of celecoxib pharmacodynamics in pancreatic cancer

Jimeno

Amador

Kulesza

et al. 2006

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Cyclooxygenase-2 (COX-2) inhibitors are being developed as chemopreventive and anticancer agents. This study aimed to determine the biological effect of the COX-2 inhibitor celecoxib in pancreatic cancer as an early step to the further development of the agent in this disease. Eight patients scheduled for resection of an infiltrating adenocarcinoma of the pancreas were randomized to receive celecoxib at a dose of 400 mg twice daily or placebo for 5 to 15 days before the surgery. In addition, carcinomas from nine additional patients were xenografted in nude mice, expanded, and treated with vehicle or celecoxib for 28 days. Celecoxib markedly decreased the intra-tumor levels of prostaglandin E 2 in patient carcinomas and in the heterotransplanted xenografts. However, this effect did not result in inhibition of cell proliferation or microvessel density (as assessed by Ki67 and CD31 staining). In addition, a panel of markers, including bcl-2, COX-1, COX-2, and VEGF, did not change with treatment in a significant manner. Furthermore, there was no evidence of antitumor effects in the xenografted carcinomas. In summary, celecoxib efficiently inhibited the synthesis of prostaglandin E 2 both in pancreatic cancer surgical specimens and in xenografted carcinomas but did not exert evident antitumor, antiproliferative, or antiangiogenic effect as a single agent. The direct pancreatic cancer xenograft model proved to be a valuable tool for drug evaluation and biological studies and showed similar results to those observed in resected pancreatic cancer specimens. [Mol Cancer Ther 2006;5(12):3240 -7]

show abstract

Cyclooxygenase inhibitors in urinary bladder cancer:in vitroandin vivoeffects

Cited by 53 publications

References 24 publications

A Histone Deacetylase Inhibitor, OBP-801, and Celecoxib Synergistically Inhibit the Cell Growth with Apoptosis via a DR5-Dependent Pathway in Bladder Cancer Cells

A Histone Deacetylase Inhibitor, OBP-801, and Celecoxib Synergistically Inhibit the Cell Growth with Apoptosis via a DR5-Dependent Pathway in Bladder Cancer Cells

Cyclooxygenase-2 Immunoreactivity in Equine Ocular Squamous-Cell Carcinoma

Assessment of celecoxib pharmacodynamics in pancreatic cancer

Contact Info

Product

Resources

About