ArticleCancer research2010
Vorinostat and sorafenib increase CD95 activation in gastrointestinal tumor cells through a Ca(2+)-de novo ceramide-PP2A-reactive oxygen species-dependent signaling pathway.
Article in Cancer research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 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
63 citing papers in PubMed, 99 citations in OpenAlex.
- Results of a phase II trial of gemcitabine plus doxorubicin in patients with recurrent head and neck cancers: serum C₁₈-ceramide as a novel biomarker for monitoring response.Clinical cancer research : an official journal of the American Association for Cancer Research · 2011Trial
- Plasma Sphingolipid Profiling Predicts Radiosensitivity in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2026Article
- Molecular Mechanism and Research Progress of Sphingolipid Metabolism in Regulating Radiation-induced Apoptosis Using Pan-cancer Analysis.Current cancer drug targets · 2026Review
- Phase 2 Study of Sorafenib, Valproic Acid, and Sildenafil in the Treatment of Recurrent High-Grade Glioma.medRxiv : the preprint server for health sciences · 2024Article
- Natural Products and Small Molecules Targeting Cellular Ceramide Metabolism to Enhance Apoptosis in Cancer Cells.Cancers · 2023Review
- Virtual Screening in the Identification of Sirtuins' Activity Modulators.Molecules (Basel, Switzerland) · 2022Review
- Lipid Nanoparticle Delivery of Fas Plasmid Restores Fas Expression to Suppress Melanoma GrowthACS nano · 2022Article
- Review
- Article
- Vorinostat in autophagic cell death: A critical insight into autophagy-mediated, -associated and -dependent cell death for cancer prevention.Drug discovery today · 2022Review
- Article
- Comprehensive analysis of LASS6 expression and prognostic value in ovarian cancer.Journal of ovarian research · 2021Article
- Ceramide launches an acute anti-adhesion pro-migration cell signaling program in response to chemotherapy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Sorafenib Treatment and Modulation of the Sphingolipid Pathway Affect Proliferation and Viability of Hepatocellular Carcinoma In Vitro.International journal of molecular sciences · 2020Article
- Fingolimod Augments Monomethylfumarate Killing of GBM Cells.Frontiers in oncology · 2020Article
- Redox inhibition of protein phosphatase PP2A: Potential implications in oncogenesis and its progression.Redox biology · 2019Review
- The role of dihydrosphingolipids in disease.Cellular and molecular life sciences : CMLS · 2019Review
- In vitro culture with gemcitabine augments death receptor and NKG2D ligand expression on tumour cells.Scientific reports · 2019Article
- Clinical epigenetics: seizing opportunities for translation.Nature reviews. Genetics · 2019Review
- Prior exposure of pancreatic tumors to [sorafenib + vorinostat] enhances the efficacy of an anti-PD-1 antibody.Cancer biology & therapy · 2019Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
The targeted therapeutics sorafenib and vorinostat interact in a synergistic fashion to kill carcinoma cells by activating CD95, and this drug combination is entering phase I evaluation. In this study, we determined how CD95 is activated by treatment with this drug combination. Low doses of sorafenib and vorinostat, but not the individual drugs, rapidly increased reactive oxygen species (ROS), Ca(2+), and ceramide levels in gastrointestinal tumor cells. The production of ROS was reduced in Rho zero cells. Quenching ROS blocked drug-induced CD95 surface localization and apoptosis. ROS generation, CD95 activation, and cell killing was also blocked by quenching of induced Ca(2+) levels or by inhibition of PP2A. Inhibition of acidic sphingomyelinase or de novo ceramide generation blocked the induction of ROS; however, combined inhibition of both acidic sphingomyelinase and de novo ceramide generation was required to block the induction of Ca(2+). Quenching of ROS did not affect drug-induced ceramide/dihydro-ceramide levels, whereas quenching of Ca(2+) reduced the ceramide increase. Sorafenib and vorinostat treatment radiosensitized liver and pancreatic cancer cells, an effect that was suppressed by quenching ROS or knockdown of LASS6. Further, sorafenib and vorinostat treatment suppressed the growth of pancreatic tumors in vivo. Our findings show that induction of cytosolic Ca(2+) by sorafenib and vorinostat is a primary event that elevates dihydroceramide levels, each essential steps in ROS generation that promotes CD95 activation.
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.