Adenovirus-mediated IKKβKA expression sensitizes prostate carcinoma cells to TRAIL-induced apoptosis

Şanlioğlu, Ahter Dilşad; Koksal, Ismail Turker; Karaçay, Bahri; Baykara, Mehmet; Lülecı, Güven; Şanlıoğlu, Salih

doi:10.1038/sj.cgt.7700877

Cited by 42 publications

(34 citation statements)

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“…15 In addition, high levels of DcR2 expression were not restricted only to the prostate cancer cell lines, but a similar correlation was also observed in patients with prostate carcinoma. 28 Thus, the current study was initiated to directly investigate the connection between high DcR2 expression and TRAIL resistance.…”

Section: Trail Expression Following Ad5htrail Infection Does Not Overmentioning

confidence: 54%

“…DR4, DR5, DcR1 and DcR2 primer and probe sequences were reported previously by our group. 13,15,26 Ribosomal RNA (rRNA) primers and probe were purchased from PE Applied Biosystems (Cat. 4308329), and served as an internal control in the same reaction.…”

Section: Gene Therapy Vectors and Cell Linesmentioning

confidence: 99%

“…Significant levels of both TRAIL death receptors, DR4 and DR5 and the decoy receptor, DcR2, were detectable on the surface, similar to that reported previously (Figure 2). 15 Because DU145 is TRAIL-resistant, siRNA-specific for DcR2 was used to determine the potential protective effect of DcR2 expression against TRAIL. Quantitative RT-PCR analysis confirmed an 8076% decrease in DcR2 mRNA expression following DcR2 siRNA treatment (data not shown).…”

Section: Sirna-mediated Downregulation Of Dcr2 Expression Sensitizes mentioning

confidence: 99%

“…13 17-allylamino-17-demethoxygeldanamycin inhibition of nuclear factor kappa B signaling sensitizes lung cancer cells to TRAIL. 14 Similarly, nuclear factor kappa B inhibition using a gene therapy approach (AdIKKbKA) 15 or curcumin 16 can sensitize hormonerefractory prostate cancer cells to TRAIL-induced apoptosis. The downregulation of the antiapoptotic proteins, such as FLICE-inhibitory protein and survivin, by various techniques (such as using the antidiabetic drug troglitazone) also sensitizes human cancer cells to TRAIL-induced apoptosis.…”

Section: Introductionmentioning

confidence: 99%

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DcR2 (TRAIL-R4) siRNA and adenovirus delivery of TRAIL (Ad5hTRAIL) break down in vitro tumorigenic potential of prostate carcinoma cells

et al. 2007

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High levels of decoy receptor 2 (DcR2; TRAIL-R4) expression are correlated with TRAIL resistance in prostate cancer cells. In addition, upregulation of TRAIL death receptor (DR4 and DR5) expression, either by ionizing radiation or chemotherapy, can sensitize cancer cells to TRAIL. Considering more than half of human cancers are TRAIL resistant, modulation of surface TRAIL receptor expression appears to be an attractive treatment modality to counteract TRAIL resistance. In this study, three siRNA duplexes targeting DcR2 receptor were tested. Ad5hTRAIL infections were performed to overexpress human full-length TRAIL to induce cell death, and the in vitro tumorigenic potential of prostate cancer cells was assessed using colony-forming assays on soft agar. The DU145 and LNCaP prostate cancer cell lines, which express high levels of DcR2, were resistant to Ad5hTRAIL-induced death. Downregulation of surface DcR2 expression by siRNA sensitized these prostate cancer cell lines to Ad5hTRAIL. In addition, DcR2 siRNA-mediated knockdown of DcR2, followed by Ad5hTRAIL infection, dramatically reduced the in vitro tumorigenic potential of prostate cancer cells. Collectively, our results suggest the potential for combining receptor-specific siRNA with TRAIL in the treatment of certain cancers.

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Section: Trail Expression Following Ad5htrail Infection Does Not Overmentioning

confidence: 54%

Section: Gene Therapy Vectors and Cell Linesmentioning

confidence: 99%

Section: Sirna-mediated Downregulation Of Dcr2 Expression Sensitizes mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

DcR2 (TRAIL-R4) siRNA and adenovirus delivery of TRAIL (Ad5hTRAIL) break down in vitro tumorigenic potential of prostate carcinoma cells

et al. 2007

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“…14,29 Thus, TRAIL-R4 might protect cells from TRAIL-induced DNA damage by either acting as a decoy receptor or transducing an antiapoptotic signal. Currently, the intracellular signaling pathways responsible for TRAIL receptor-mediated NF-kB activation are unclear, and the mechanisms responsible for TRAIL receptor-induced apoptosis are controversial.…”

Section: Trail Pathway In Varicocele-induced Testesmentioning

confidence: 99%

Role of TNF-related apoptosis-inducing ligand (TRAIL) in the pathogenesis of varicocele-induced testicular dysfunction

Çelik¹,

Kutlu²,

Tekcan³

et al. 2012

Asian J Androl

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The higher frequency of varicocele in men with infertility has drawn attention and resulted in increased research at the molecular level towards treatments. The aim of this study was to investigate the role of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and its receptors in varicocele-induced testicular dysfunction in an experimental rat model. The rats were divided into three groups: control, sham and varicocele. Varicoceles in rats were induced by partial ligation of the left renal vein and left testes. The rats were analyzed 13 weeks after surgery. The degree of DNA fragmentation within cells in the testis was determined using terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling (TUNEL) assay. Tubule degeneration was evaluated using the Johnsen score. The expression of TRAIL and its receptors was detected by immunohistochemical and Western blotting techniques. The apoptotic index, Johnsen score and the expression of TRAIL and TRAIL receptors were examined. The data are presented as the mean6s.d. and were analyzed using computer software. The Kruskal-Wallis and Dunn's multiple comparison tests were used in the statistical analyses. The germ cell apoptotic index was increased in rats with varicoceles when compared with the sham and control groups (P50.0031). The Johnsen score was significantly decreased in the varicocele group when compared with the sham and control groups (P,0.0001). Immunohistochemical and Western blotting analyses showed that after varicocele induction, the expression of TRAIL-R1 and TRAIL-R4 in germ cells was increased and the expression of TRAIL-R2 was decreased. There are no significant differences among the groups in terms of TRAIL and TRAIL-R3 receptor expression. The results of this study indicate that TRAIL and its receptors may have a potential role in the pathogenesis of varicocele-induced testicular dysfunction.

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The TRAIL of oncogenes to apoptosis

Oikonomou

Pintzas

2013

BioFactors

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Despite the significant advances in clinical research, surgical resection, radiotherapy and chemotherapy are still used as the primary method for cancer treatment. As compared to conventional therapies that often induce systemic toxicity and eventually contribute to tumor resistance, the TNF-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent that selectively triggers apoptosis in various cancer cells by interacting with its proapoptotic receptors DR4 and KILLER/DR5, while sparing the normal surrounding tissue. The intensive studies of TRAIL signaling pathways over the past decade have provided clues for understanding the molecular mechanisms of TRAIL-induced apoptosis in carcinogenesis and identified an array of therapeutic responses elicited by TRAIL and its receptor agonists. Analysis of its activity at the molecular level has shown that TRAIL improves survival either as monotherapies or combinatorial therapies with other mediators of apoptosis or anticancer chemotherapy. Combinatorial treatments amplify the activities of anticancer agents and widen the therapeutic window by overcoming tumor resistance to apoptosis and driving cancer cells to self-destruction. Although TRAIL sensitivity varies widely depending on the cell type, nontransformed cells are largely resistant to death mediated by TRAIL Death Receptors (DRs). Genetic alterations in cancer can contribute in tumor progression and often play an important role in evasion of apoptosis by tumor cells. Remarkably, RAS, MYC and HER2 oncogenes have been shown to sensitise tumor cells to TRAIL induced cell death. Here, we summarise the cross-talk of oncogenic and apoptotic pathways and how they can be exploited toward efficient combinatorial therapeutic protocols.

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Adenovirus-mediated IKKβKA expression sensitizes prostate carcinoma cells to TRAIL-induced apoptosis

Cited by 42 publications

References 42 publications

DcR2 (TRAIL-R4) siRNA and adenovirus delivery of TRAIL (Ad5hTRAIL) break down in vitro tumorigenic potential of prostate carcinoma cells

DcR2 (TRAIL-R4) siRNA and adenovirus delivery of TRAIL (Ad5hTRAIL) break down in vitro tumorigenic potential of prostate carcinoma cells

Role of TNF-related apoptosis-inducing ligand (TRAIL) in the pathogenesis of varicocele-induced testicular dysfunction

The TRAIL of oncogenes to apoptosis

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