ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009
Acid ceramidase upregulation in prostate cancer cells confers resistance to radiation: AC inhibition, a potential radiosensitizer.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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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
68 citing papers in PubMed, 118 citations in OpenAlex.
- Acid ceramidase modulates the lipid profile and exacerbates sensitivity to ferroptosis in WI-38 replicative senescent cells.Cell death & disease · 2026Article
- Acid ceramidase modulates the lipid profile and exacerbates sensitivity to ferroptosis in senescent cells.Research square · 2025Article
- Lipids: Driving Forces in the Underlying Biology of Carcinogenesis.ACS pharmacology & translational science · 2025Review
- Sphingolipid signaling in kidney diseases.American journal of physiology. Renal physiology · 2025Review
- Therapeutic Potential of Ceramide in Cancer Treatment.Journal of cancer research and oncobiology · 2024Article
- High-throughput discovery of novel small-molecule inhibitors of acid Ceramidase.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Natural Products and Small Molecules Targeting Cellular Ceramide Metabolism to Enhance Apoptosis in Cancer Cells.Cancers · 2023Review
- Review
- Advances in Hybrid Vesicular-based Drug Delivery Systems: Improved Biocompatibility, Targeting, Therapeutic Efficacy and Pharmacokinetics of Anticancer Drugs.Current drug metabolism · 2022Article
- Inhibition of acid ceramidase elicits mitochondrial dysfunction and oxidative stress in pancreatic cancer cells.Cancer science · 2021Article
- Acid ceramidase controls apoptosis and increases autophagy in human melanoma cells treated with doxorubicin.Scientific reports · 2021Article
- Ablation of Acid Ceramidase Impairs Autophagy and Mitochondria Activity in Melanoma Cells.International journal of molecular sciences · 2021Article
- Review
- Implications of Sphingolipids on Aging and Age-Related Diseases.Frontiers in aging · 2021Review
- The Role of Sphingolipids Metabolism in Cancer Drug Resistance.Frontiers in oncology · 2021Review
- Design, Synthesis, and Biological Evaluation of a Series of Oxazolone Carboxamides as a Novel Class of Acid Ceramidase Inhibitors.Journal of medicinal chemistry · 2020Article
- Article
- Inhibition of acid ceramidase regulates MHC class II antigen presentation and suppression of autoimmune arthritis.Cytokine · 2020Article
- Sphingolipid Metabolism in Glioblastoma and Metastatic Brain Tumors: A Review of Sphingomyelinases and Sphingosine-1-Phosphate.Biomolecules · 2020Review
- Review
8 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
20 authors at 2 institutions in 2 countries.
Funding
Abstract
Radiation resistance in a subset of prostate tumors remains a challenge to prostate cancer radiotherapy. The current study on the effects of radiation on prostate cancer cells reveals that radiation programs an unpredicted resistance mechanism by upregulating acid ceramidase (AC). Irradiated cells demonstrated limited changes of ceramide levels while elevating levels of sphingosine and sphingosine-1-phosphate. By genetically downregulating AC with small interfering RNA (siRNA), we observed radiosensitization of cells using clonogenic and cytotoxicity assays. Conversely, AC overexpression further decreased sensitivity to radiation. We also observed that radiation-induced AC upregulation was sufficient to create cross-resistance to chemotherapy as demonstrated by decreased sensitivity to Taxol and C(6) ceramide compared to controls. Lower levels of caspase 3/7 activity were detected in cells pretreated with radiation, also indicating increased resistance. Finally, utilization of the small molecule AC inhibitor, LCL385, sensitized PPC-1 cells to radiation and significantly decreased tumor xenograft growth. These data suggest a new mechanism of cancer cell resistance to radiation, through upregulation of AC that is, in part, mediated by application of the therapy itself. An improved understanding of radiotherapy and the application of combination therapy achieved in this study offer new opportunities for the modulation of radiation effects in the treatment of cancer.
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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.