ArticleBiochemistry and cell biology = Biochimie et biologie cellulaire2012
Dihydroceramide accumulation and reactive oxygen species are distinct and nonessential events in 4-HPR-mediated leukemia cell death.
Article in Biochemistry and cell biology = Biochimie et biologie cellulaire, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- Fenretinide in cancer therapy and chemoprevention: past, present and future.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Preclinical evaluation of fenretinide against primary and metastatic intestinal type‑gastric cancer.Oncology letters · 2024Article
- Tailoring photocatalysts to modulate oxidative potential of anilides enhances para-selective electrochemical hydroxylation.Nature communications · 2024Article
- Pretreatment of human retinal pigment epithelial cells with sterculic acid forestalls fenretinide-induced apoptosis.Scientific reports · 2022Article
- Fenretinide in Cancer and Neurological Disease: A Two-Face Janus Molecule.International journal of molecular sciences · 2022Review
- Bovine Dialyzable Leukocyte Extract IMMUNEPOTENT-CRP Induces Selective ROS-Dependent Apoptosis in T-Acute Lymphoblastic Leukemia Cell Lines.Journal of oncology · 2020Article
- Selenium protects against LPS-induced MC3T3-E1 cells apoptosis through modulation of microRNA-155 and PI3K/Akt signaling pathways.Genetics and molecular biology · 2020Article
- Approaches for probing and evaluating mammalian sphingolipid metabolism.Analytical biochemistry · 2019Review
- Lipid Metabolism in Late-Onset Alzheimer's Disease Differs from Patients Presenting with Other Dementia Phenotypes.International journal of environmental research and public health · 2019Article
- The role of dihydrosphingolipids in disease.Cellular and molecular life sciences : CMLS · 2019Review
- Probing de novo sphingolipid metabolism in mammalian cells utilizing mass spectrometry.Journal of lipid research · 2018Article
- Lipophagy prevents activity-dependent neurodegeneration due to dihydroceramide accumulationEMBO reports · 2017Article
- Synthesis and Antiproliferative Activity of Novel All-Trans-Retinoic Acid-Podophyllotoxin Conjugate towards Human Gastric Cancer Cells.Molecules (Basel, Switzerland) · 2017Article
- Dihydroceramides: From Bit Players to Lead Actors.The Journal of biological chemistry · 2015Review
- Role of Sphingolipids and Metabolizing Enzymes in Hematological Malignancies.Molecules and cells · 2015Review
- Inhibition of dihydroceramide desaturase activity by the sphingosine kinase inhibitor SKI II.Journal of lipid research · 2014Article
- Modulation of oxidative stress as an anticancer strategy.Nature reviews. Drug discovery · 2013Review
- C22:0- and C24:0-dihydroceramides confer mixed cytotoxicity in T-cell acute lymphoblastic leukemia cell lines.PloS one · 2013Article
- Novel chemotherapeutic drugs in sphingolipid cancer research.Handbook of experimental pharmacology · 2013Review
- Inhibition of sphingolipid metabolism enhances resveratrol chemotherapy in human gastric cancer cells.Biomolecules & therapeutics · 2012Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
4-(Hydroxyphenyl)retinamide (4-HPR) is a synthetic retinoid with a strong apoptotic effect towards different cancer cell lines in vitro, and it is currently tested in clinical trials. Increases of reactive oxygen species (ROS) and modulation of endogenous sphingolipid levels are well-described events observed upon 4-HPR treatment, but there is still a lack of understanding of their relationship and their contribution to cell death. LC-MS analysis of sphingolipids revealed that in human leukemia CCRF-CEM and Jurkat cells, 4-HPR induced dihydroceramide but not ceramide accumulation even at sublethal concentrations. Myriocin prevented the 4-HPR-induced dihydroceramide accumulation, but it did not prevent the loss of viability and increase of intracellular ROS production. On the other hand, ascorbic acid, Trolox, and vitamin E reversed 4-HPR effects on cell death but not dihydroceramide accumulation. NDGA, described as a lipoxygenase inhibitor, exerted a significantly higher antioxidant activity than vitamin E and abrogated 4-HPR-mediated ROS. It did not however rescue cellular viability. Taken together, this study demonstrates that early changes observed upon 4-HPR treatment, i.e., sphingolipid modulation and ROS production, are mechanistically independent events. Furthermore, the results indicate that 4-HPR-driven cell death may occur even in the absence of dihydroceramide or ROS accumulation. These observations should be taken into account for an improved design of drug combinations.
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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.