Celecoxib and a novel COX-2 inhibitor ON09310 upregulate death receptor 5 expression via GADD153/CHOP

He, Qiaojun; Luo, Xuelian; Jin, Weixin; Huang, Ying; Reddy, Meera; Reddy, E. Premkumar; Sheikh, M. Saeed

doi:10.1038/sj.onc.1210894

Cited by 39 publications

(25 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have reported that celecoxib induced apoptosis via upregulation of DR5 in several cancer cells (22,23). However, in this study, celecoxib alone did not induce apoptosis ( Fig.…”

Section: Discussioncontrasting

confidence: 54%

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: Discussioncontrasting

confidence: 54%

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

“…In line with earlier studies (37-39) we find increased TRAIL-R2 surface expression on bortezomib treatment. TRAIL receptor expression can be transcriptionally upregulated by the endoplasmic reticulum-stress related protein CHOP (40), by NFkB (41) and p53 (42). However, we do not detect any changes in the total amount of TRAIL-R2 protein in whole cell lysates, indicating that bortezomib may trigger increased TRAIL-R2 surface expression without detectable changes in total protein expression of TRAIL-R2 in glioblastoma cells.…”

Section: Discussioncontrasting

confidence: 45%

Bortezomib Primes Glioblastoma, Including Glioblastoma Stem Cells, for TRAIL by Increasing tBid Stability and Mitochondrial Apoptosis

Unterkircher

Cristofanon²,

Vellanki³

et al. 2011

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Searching for novel approaches to sensitize glioblastoma for cell death, we investigated the proteasome inhibitor bortezomib.Experimental Design: The effect of bortezomib on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis signaling pathways was analyzed in glioblastoma cell lines, primary glioblastoma cultures, and in an in vivo model.Results: Bortezomib and TRAIL synergistically trigger cell death and reduce colony formation of glioblastoma cells (combination index < 0.1). Investigations into the underlying molecular mechanisms reveal that bortezomib and TRAIL act in concert to cause accumulation of tBid, the active cleavage product of Bid. Also, the stability of TRAIL-derived tBid markedly increases on proteasome inhibition. Notably, knockdown of Bid significantly decreases bortezomib-and TRAIL-mediated cell death. By comparison, silencing of Noxa, which is also upregulated by bortezomib, does not confer protection. Coinciding with tBid accumulation, the activation of Bax/Bak and loss of mitochondrial membrane potential are strongly increased in cotreated cells. Overexpression of Bcl-2 significantly reduces mitochondrial perturbations and cell death, underscoring the functional relevance of the mitochondrial pathway. In addition, bortezomib cooperates with TRAIL to reduce colony formation of glioblastoma cells, showing an effect on long-term survival. Of note, bortezomib profoundly enhances TRAIL-triggered cell death in primary cultured glioblastoma cells and in patient-derived glioblastoma stem cells, underlining the clinical relevance. Importantly, bortezomib cooperates with TRAIL to suppress tumor growth in an in vivo glioblastoma model.Conclusion: These findings provide compelling evidence that the combination of bortezomib and TRAIL presents a promising novel strategy to trigger cell death in glioblastoma, including glioblastoma stem cells, which warrants further investigation. Clin Cancer Res; 17(12); 4019-30. Ó2011 AACR.

show abstract

“…In addition, tumor metastases and invasion occur when the TRAIL-induced apoptosis pathway is impeded (11,16,37). Recent studies suggested that inhibition of COX-2 increased the sensitivity of hepatocellular carcinoma cells to TRAIL (17,38,39). In this study, our data showed that Ad-TM showed dramatic hepatocellular carcinoma cytotoxicity via COX-2 gene silencing coupled with TRAIL expression in both in vitro and in vivo conditions.…”

Section: Discussionsupporting

confidence: 53%

Potent Antitumor Activity in Experimental Hepatocellular Carcinoma by Adenovirus-Mediated Coexpression of TRAIL and shRNA against COX-2

Chen

Lou

Shen

et al. 2010

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Recent studies have indicated that short hairpin RNA (shRNA) driven by RNA polymerase (Pol) II promoters can be transcribed into precursor mRNAs together with transgenes. It remains unclear, however, whether coexpression of shRNA and transgene from a single promoter is feasible for cancer therapy.Experimental Design: In this study, we generated novel adenoviral vectors that permitted coexpression of shRNA against cyclooxygenase-2 (COX-2) and the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) therapeutic gene from a cytomegalovirus promoter to evaluate whether silencing of COX-2 could increase the sensitivity of hepatocellular carcinoma to TRAIL.Results: Our data showed that adenovirus vector Ad-TM, in which the shRNA was inserted into the 3′ untranslated region of the TRAIL gene, not only significantly suppressed COX-2 expression, but also expressed a high level of TRAIL. Moreover, infection with Ad-TM resulted in significant cytotoxicity in hepatocellular carcinoma cell lines. In contrast, it had no effect on normal liver cell line. Impressively, treatment of the established hepatocellular carcinoma tumors with Ad-TM resulted in complete tumor regression. This potent antitumor activity induced by Ad-TM was due to strong inhibition of COX-2 and high expression of TRAIL. Furthermore, using the shRNA and transgene coexpression adenovirus system, we showed that silencing of COX-2 increased the sensitivity of hepatocellular carcinoma to TRAIL through inhibition of Bcl-2 and Bcl-w.Conclusion: This study indicated that adenovirus carrying shRNA and transgene expressed from a single promoter represented a potent approach for cancer therapy.

show abstract

Celecoxib and a novel COX-2 inhibitor ON09310 upregulate death receptor 5 expression via GADD153/CHOP

Cited by 39 publications

References 13 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

Bortezomib Primes Glioblastoma, Including Glioblastoma Stem Cells, for TRAIL by Increasing tBid Stability and Mitochondrial Apoptosis

Potent Antitumor Activity in Experimental Hepatocellular Carcinoma by Adenovirus-Mediated Coexpression of TRAIL and shRNA against COX-2

Contact Info

Product

Resources

About