Combination of vorinostat and adenovirus-TRAIL exhibits a synergistic antitumor effect by increasing transduction and transcription of TRAIL in lung cancer cells

Dr, Kim; Park, MY; Cs, Lee; Shim, Seung‐Hyuk; Hi, Yoon; Jh, Lee; Mw, Sung; Ys, Kim; Ct, Lee

doi:10.1038/cgt.2011.11

Cited by 16 publications

(15 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…44 In our library of 1200 drugs, there was only one HDAC inhibitor, Vorinostat, which was previously indicated as an anti-cancer agents and also studied as a TRAIL sensitizing agent in various cancers including leukemia and lung cancer. 43,45,46 Consistent with these observations, Vorinostat cooperated with TRAIL and scored as a hit in our screen, highlighting the validity of our screen findings. Given the growing interest in the field of epigenetic enzyme inhibitors as therapies, Vorinostat and TRAIL combination can also offer promise in the future for GBMs.…”

Section: Discussionsupporting

confidence: 86%

Identification of Mitoxantrone as a TRAIL-sensitizing agent for Glioblastoma Multiforme

Senbabaoglu

Cingöz

Kaya

et al. 2016

Cancer Biology & Therapy

View full text Add to dashboard Cite

Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) has tremendous promise in treating various forms of cancers. However, many cancer cells exhibit or develop resistance to TRAIL. Interestingly, many studies have identified several secondary agents that can overcome TRAIL resistance. To expand on these studies, we conducted an extensive drug-re-profiling screen to identify FDA-approved compounds that can be used clinically as TRAIL-sensitizing agents in a very malignant type of brain cancer, Glioblastoma Multiforme (GBM). Using selected isogenic GBM cell pairs with differential levels of TRAIL sensitivity, we revealed 26 TRAIL-sensitizing compounds, 13 of which were effective as single agents. Cardiac glycosides constituted a large group of TRAIL-sensitizing compounds, and they were also effective on GBM cells as single agents. We then explored a second class of TRAIL-sensitizing drugs, which were enhancers of TRAIL response without any effect on their own. One such drug, Mitoxantrone, a DNAdamaging agent, did not cause toxicity to non-malignant cells at the doses that synergized with TRAIL on tumor cells. We investigated the downstream changes in apoptosis pathway components upon Mitoxantrone treatment, and observed that Death Receptors (DR4 and DR5) expression was upregulated, and pro-apoptotic and anti-apoptotic gene expression patterns were altered in favor of apoptosis. Together, our results suggest that combination of Mitoxantrone and TRAIL can be a promising therapeutic approach for GBM patients.

show abstract

Section: Discussionsupporting

confidence: 86%

Identification of Mitoxantrone as a TRAIL-sensitizing agent for Glioblastoma Multiforme

Senbabaoglu

Cingöz

Kaya

et al. 2016

Cancer Biology & Therapy

View full text Add to dashboard Cite

show abstract

“…6A and B). This finding is consistent with our previous experiment that vorinostat showed a dual effect on adenoviral gene expression by increasing transduction through elevated CAR and by increasing transcription of the adenoviral transgene (12). Δ24 on lung cancer cells.…”

Section: Pre-or Post-transductional Vorinostat Increases Luciferase Esupporting

confidence: 93%

“…Many HDAC inhibitors have been reported to augment adenoviral gene therapy by enhancing CAR expression (7)(8)(9)(10). Furthermore, HDAC inhibitors were found to enhance the transcription of adenoviral transgenes in target cells (11,12). Strong synergistic interactions were found in various HDAC inhibitors and adenoviruses with the therapeutic gene (7,8,12).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Combination therapy of conditionally replicating adenovirus and histone deacetylase inhibitors

Lee¹

2011

Int J Mol Med

View full text Add to dashboard Cite

Abstract. Combination therapy of adenoviral gene therapy and a histone deacetylase (HDAC) inhibitor is important due to the enhancing effect of HDAC inhibitors on adenoviral transduction and transcription. However, contradictory results have been reported on the effect of combination of CRAd (conditionally replicating adenovirus) and HDAC inhibitors. This study was designed to investigate the interaction of CRAd and HDAC inhibitors and determine the ideal way to combine the two agents. Combination of HDAC inhibitors (SK7041, SBHA and vorinostat) at pre-and post-transductional periods with CRAd enhanced the transduction of CRAd and expression of luciferase expression from Δ24-luc in vitro. However, suppression of luciferase expression from Δ24-luc injected tumor mass was observed by in vivo tumor bioluminescence imaging and drug interaction analysis also showed an antagonistic interaction that was probably related with the inhibitory effect of the HDAC inhibitor on adenoviral replication. Suppression of p21 induction by p21 siRNA reversed the suppressive effect of vorinostat on the replication of CRAd, but still failed to reverse the antagonistic interaction. Addition of vorinostat at the pre-transductional period revealed an improvement in the transduction efficiency of CRAd and also induced a synergistic interaction between CRAd and vorinostat, which was possibly related with prevention of the suppressive effect of vorinostat on adenoviral replication. In conclusion, the addition of HDAC inhibitor before CRAd injection showed synergistic antitumor effects, which warrants further investigation on the sequence of HDAC inhibitor and CRAd treatment in an animal tumor model.

show abstract

“…In our study, AdTRAIL had a dose-dependent cytotoxic effect in NSCLC cell lines, and this effect became significant at high MOL Previous studies have often focused on enhancing the activity of AdTRAIL by increasing the transduction and transcription of TRAIL in lung cancer cells[28]. However, because normal human liver cells and certain epithelial cells are susceptible to recombinant TRAIL proteins [26] serious concerns about the potential toxicity of high-dose TRAIL protein administered systemically have been raised.…”

Section: Discussionmentioning

confidence: 56%

EGFR inhibitors sensitize non-small cell lung cancer cells to TRAIL-induced apoptosis

Tian²,

Huang³

et al. 2011

Chin J Cancer

View full text Add to dashboard Cite

Apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can be regulated by the epidermal growth factor (EGF) signaling pathway. In this study, recombinant adenoviral vectors that encode TRAIL gene from the hTERT/RGD promoter (AdTRAIL) was combined with drugs including gefitinib, elotinib, and cetuximab that inhibit EGFR and the EGF signaling pathway in non–small cell lung cancer (NSCLC) cell lines to investigate their antitumor activity. In vitro, compared to single reagent, AdTRAIL combined with EGFR inhibitors reduced proliferation and enhanced apoptosis in H460, A549, and SW1573 cell lines. Western blot results suggested that these effects were relative to upregulation of pro-apoptosis protein BAX and down-regulation of p-AKT. In vivo, AdTRAIL combined with cetuximab resulted in a significant growth reduction in H460 xenografts without damage to the main organs of nude mice. Histological examination and TUNEL analyses of xenografts showed that cetuximab enhanced cell apoptosis induced by AdTRAIL. These results indicate that EGFR inhibitors enhanced AdTRAIL anti-tumor activity in NSCLC cell lines and that inhibiting the AKT pathway played an important role in this enhancement.

show abstract

Combination of vorinostat and adenovirus-TRAIL exhibits a synergistic antitumor effect by increasing transduction and transcription of TRAIL in lung cancer cells

Cited by 16 publications

References 24 publications

Identification of Mitoxantrone as a TRAIL-sensitizing agent for Glioblastoma Multiforme

Identification of Mitoxantrone as a TRAIL-sensitizing agent for Glioblastoma Multiforme

Combination therapy of conditionally replicating adenovirus and histone deacetylase inhibitors

EGFR inhibitors sensitize non-small cell lung cancer cells to TRAIL-induced apoptosis

Contact Info

Product

Resources

About