Targeting Death Receptors in Bladder, Prostate and Renal Cancer

O'Kane, Hugh F.; Watson, Chris; Johnston, S. R.; Peták, István; William, R.; Watson, G.; Williamson, Kate E.

doi:10.1016/s0022-5347(05)00160-6

Cited by 44 publications

(41 citation statements)

References 51 publications

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“…Caspases are critical protease mediators of apoptosis triggered by different stimuli including TRAIL (9,34,35). In the present study, we found that in T24 and 253j cells treated with the combination of mapatumumab and EPI, the initiative caspases such as caspase-8, -9 and effective caspases including caspase-3 were significantly activated.…”

Section: Discussionsupporting

confidence: 51%

Synergistic induction of apoptosis by mapatumumab and anthracyclines in human bladder cancer cells

Ahmed

Jin

et al. 2014

Oncology Reports

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Abstract. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in a variety of tumor cells by engaging the death receptors 4 (DR4) and 5 (DR5). We investigated the effect of chemotherapeutic drugs on DR4-mediated apoptosis in human bladder cancer cells, using a human monoclonal agonistic antibody specific for DR4, mapatumumab. Cytotoxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Synergy was assessed by isobolographic analysis. Treatment of human bladder cancer T24 cells with mapatumumab in combination with mitomycin C, vinblastine or gemcitabine did not overcome resistance to these agents. However, treatment with mapatumumab in combination with epirubicin (EPI) had a synergistic cytotoxic effect. Synergy was also obtained in KU7 and RT112 human bladder cancer cells. A synergistic effect was also observed with mapatumumab in combination with pirarubicin. The synergy obtained in cytotoxicity with mapatumumab and EPI was also achieved in apoptosis. EPI markedly increased DR4 expression in the bladder cancer cells at both the mRNA and protein levels. Furthermore, the combination-induced cytotoxicity was significantly suppressed by the DR4:Fc chimeric protein. The combination of EPI and mapatumumab significantly activated the caspase cascade, including caspase-8, -9 and -3, which are the downstream molecules of death receptors. These findings indicate that EPI sensitizes bladder cancer cells to DR4-mediated apoptosis through induction of DR4 and activation of caspases, suggesting that the combination therapy of EPI and mapatumumab may be effective for bladder cancer therapy. IntroductionEach year more than 350,000 new cases of bladder cancer are diagnosed globally (1), making bladder cancer the ninth most frequent cancer worldwide (2). Epirubicin (EPI) and pirarubicin (THP) are a new generation of anthracycline drugs, widely used as anticancer chemotherapeutic agents in various types of cancers including bladder cancer (2,3). Furthermore, these anthracycline drugs are less cardiotoxic than doxorubicin. However intrinsic and acquired resistance to chemotherapeutic drugs are considered as major problems. Therefore, it is important to develop new treatment strategies for bladder cancer patients to prevent recurrence and reduce the risk of tumor progression.Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a pro-apoptotic member of the TNF superfamily and a potentially effective anticancer agent. TRAIL has been identified as a powerful activator of programmed cell death or apoptosis in various tumor cells, yet is considered relatively nontoxic against most normal cells (4-6). TRAIL induces apoptosis by interacting with two death-inducing receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5) following activation of the caspase cascade that initiates both extrinsic and intrinsic apoptotic pathways (4,7-9). In addition, TRAIL binds to two other receptors, TRAIL-R3 (DcR1) and TRAIL-R4 (DcR2), which lack a functional cytoplasmic death dom...

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Section: Discussionsupporting

confidence: 51%

Synergistic induction of apoptosis by mapatumumab and anthracyclines in human bladder cancer cells

Ahmed

Jin

et al. 2014

Oncology Reports

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“…Korkolopoulou and colleagues reported that expression of FLIP in bladder cancer has been associated with advanced stage and grade (24). Therefore, it is expected that FLIP might be as an indicator of prognosis (25). Several studies have also shown that HDAC inhibitors can reduce the expression of FLIP (26,27).…”

Section: Discussionmentioning

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

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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.

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“…Sensitivity to rTRAIL-induced apoptosis was reported in cell lines derived from human colon, lung, breast, kidney, brain and skin cancer (Ashkenazi et al, 1999). Till date, effective apoptosis induction by rTRAIL has been reported in human melanoma, leukemia, multiple myeloma, breast, bladder, prostate, renal or colon cancer in single treatments and/or combination therapy with chemotherapeutic agents (Chawla-Sarkar et al, 2002;An et al, 2003;Buchsbaum et al, 2003;van Geelen et al, 2003;VoelkelJohnson, 2003;Merchant et al, 2004;Georgakis et al, 2005;Kaufmann and Steensma, 2005;Kurbanov et al, 2005;Pukac et al, 2005;Bucur et al, 2006;Marini et al, 2006;O'Kane et al, 2006;Zeng et al, 2006). Thus, these cancers are the most promising indications for clinical trials of TRAIL and anti-DR5/DR4 mAb.…”

Section: Clinical Applicationmentioning

confidence: 99%

Targeting death-inducing receptors in cancer therapy

et al. 2007

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Deregulated cell death pathways may lead to the development of cancer, and induction of tumor cell apoptosis is the basis of many cancer therapies. Knowledge accumulated concerning the molecular mechanisms of apoptotic cell death has aided the development of new therapeutic strategies to treat cancer. Signals through death receptors of the tumor necrosis factor (TNF) superfamily have been well elucidated, and death receptors are now one of the most attractive therapeutic targets in cancer. In particular, DR5 and DR4, death receptors of TNF-related apoptosis-inducing ligand (TRAIL or Apo2L), are interesting targets of antibody-based therapy, since TRAIL may also bind decoy receptors that may prevent TRAIL-mediated apoptosis, whereas TRAIL ligand itself selectively induces apoptosis in cancer cells. Here, we review the potential therapeutic utility of agonistic antibodies against DR5 and DR4 and discuss the possible extension of this single-antibody-based strategy when combined with additional modalities that either synergizes to cause enhanced apoptosis or further engage the cellular immune response. Rational design of antibody-based therapies combining the induction of tumor cell apoptosis and activation of tumor-specific adaptive immunity enables promotion of distinct steps of the antitumor immune response, thereby enhancing tumorspecific lymphocytes that can eradicate TRAIL/DR5-resistant mutating, large established and heterogeneous tumors in a manner that does not require the definition of individual tumor-specific antigens.

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Targeting Death Receptors in Bladder, Prostate and Renal Cancer

Cited by 44 publications

References 51 publications

Synergistic induction of apoptosis by mapatumumab and anthracyclines in human bladder cancer cells

Synergistic induction of apoptosis by mapatumumab and anthracyclines in human 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

Targeting death-inducing receptors in cancer therapy

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