ArticleOncogene2016
Critical role of mitochondria-mediated apoptosis for JNJ-26481585-induced antitumor activity in rhabdomyosarcoma.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 35 citations in OpenAlex.
- New synergistic combination therapy approaches with HDAC inhibitor quisinostat, cisplatin or PARP inhibitor talazoparib for urothelial carcinoma.Journal of cellular and molecular medicine · 2024Article
- Article
- Staufen1 controls mitochondrial metabolism via HIF2α in embryonal rhabdomyosarcoma and promotes tumorigenesis.Cellular and molecular life sciences : CMLS · 2023Article
- Article
- A review of the therapeutic potential of histone deacetylase inhibitors in rhabdomyosarcoma.Frontiers in oncology · 2023Review
- Evidence of a non-apoptotic mode of cell death in microglial BV-2 cells exposed to different concentrations of zinc oxide nanoparticles.Environmental science and pollution research international · 2021Article
- Therapeutic Approaches Targeting PAX3-FOXO1 and Its Regulatory and Transcriptional Pathways in Rhabdomyosarcoma.Molecules (Basel, Switzerland) · 2018Review
- MEK inhibitors induce apoptosis via FoxO3a-dependent PUMA induction in colorectal cancer cells.Oncogenesis · 2018Article
- BCL-2 selective inhibitor ABT-199 primes rhabdomyosarcoma cells to histone deacetylase inhibitor-induced apoptosis.Oncogene · 2018Article
- AP-1 confers resistance to anti-cancer therapy by activating XIAP.Oncotarget · 2018Article
- Time-Dependent Effects of POT1 Knockdown on Proliferation, Tumorigenicity, and HDACi Response of SK-OV3 Ovarian Cancer Cells.BioMed research international · 2018Article
- Angelicin inhibits liver cancer growth in vitro and in vivo.Molecular medicine reports · 2017Article
- Concomitant epigenetic targeting of LSD1 and HDAC synergistically induces mitochondrial apoptosis in rhabdomyosarcoma cells.Cell death & disease · 2017Article
- Neuroblastoma cells depend on HDAC11 for mitotic cell cycle progression and survival.Cell death & disease · 2017Article
- Inhibitor of apoptosis protein expression in glioblastomas and their in vitro and in vivo targeting by SMAC mimetic GDC-0152.Cell death & disease · 2016Article
- Cooperative TRAIL production mediates IFNα/Smac mimetic-induced cell death in TNFα-resistant solid cancer cells.Oncotarget · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
JNJ-26481585 is a second-generation histone deacetylase inhibitor with broad-range efficacy and improved pharmacodynamic properties. In the present study, we investigated the therapeutic potential of JNJ-26481585 and its molecular mechanisms of action in rhabdomyosarcoma (RMS). Here, we report that JNJ- 26481585's anticancer activity critically depends on an intact mitochondrial pathway of apoptosis. JNJ-26481585 induces apoptosis and also inhibits long-term clonogenic survival of several RMS cell lines at nanomolar concentrations that cause histone acetylation. Importantly, JNJ-26481585 significantly suppresses tumor growth in vivo in two preclinical RMS models, that is, the chorioallantoic membrane model and a xenograft mouse model. Mechanistically, we identify activation of the mitochondrial pathway of apoptosis as a key event that is critically required for JNJ-26481585-mediated cell death. JNJ-26481585 upregulates expression levels of several BH3-only proteins including Bim, Puma and Noxa, which all contribute to JNJ-26481585-mediated apoptosis, as knockdown of Bim, Puma or Noxa significantly inhibits cell death. This shift toward proapoptotic Bcl-2 proteins promotes activation of Bax and Bak as a critical event, as genetic silencing of Bax or Bak protects against JNJ-26481585-induced apoptosis. Intriguingly, rescue experiments reveal that JNJ-26481585 triggers Bax/Bak activation independently of caspase activation and activates caspase-9 as the initiator caspase in the cascade, as Bcl-2 overexpression, but not the broad-range caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD.fmk) blocks JNJ-26481585-induced Bax/Bak activation and caspase-9 cleavage. In conclusion, JNJ-26481585 exerts potent antitumor activity against RMS in vitro and in vivo by engaging mitochondrial apoptosis before caspase activation and represents a promising therapeutic for further investigation in RMS.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.