ArticleMolecular cancer research : MCR2009
Potentiation of cannabinoid-induced cytotoxicity in mantle cell lymphoma through modulation of ceramide metabolism.
Article in Molecular cancer research : MCR, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Systematic review of the literature on clinical and experimental trials on the antitumor effects of cannabinoids in gliomas.Journal of neuro-oncology · 2014Pooled it
- Revealing the therapeutic potential of synthetic cannabinoids: a systematic review of cannabinoid receptor binding dynamics and their implications for cancer therapy.Journal of cannabis research · 2025Review
- Article
- Cannabinoids-Multifunctional Compounds, Applications and Challenges-Mini Review.Molecules (Basel, Switzerland) · 2024Review
- Therapeutic Potential of Ceramide in Cancer Treatment.Journal of cancer research and oncobiology · 2024Article
- The ceramide synthase (CERS/LASS) family: Functions involved in cancer progression.Cellular oncology (Dordrecht, Netherlands) · 2023Review
- Reversion of chemoresistance by endocannabinoid-induced ER stress and autophagy activation in ovarian cancer.American journal of cancer research · 2023Article
- Inhibition of Sphingosine Kinase Activity Enhances Immunogenic Cell Surface Exposure of Calreticulin Induced by the Synthetic Cannabinoid 5-epi-CP-55,940.Cannabis and cannabinoid research · 2022Article
- Sphingolipids and Lymphomas: A Double-Edged Sword.Cancers · 2022Review
- Cannabinoids in the landscape of cancer.Journal of cancer research and clinical oncology · 2021Review
- Cannabinoid Effects on Experimental Colorectal Cancer Models Reduce Aberrant Crypt Foci (ACF) and Tumor Volume: A Systematic Review.Evidence-based complementary and alternative medicine : eCAM · 2020Review
- Requirement for sphingosine kinase 1 in mediating phase 1 of the hypotensive response to anandamide in the anaesthetised mouse.European journal of pharmacology · 2019Article
- Insights into the effects of the endocannabinoid system in cancer: a review.British journal of pharmacology · 2018Review
- Anandamide Revisited: How Cholesterol and Ceramides Control Receptor-Dependent and Receptor-Independent Signal Transmission Pathways of a Lipid Neurotransmitter.Biomolecules · 2018Review
- Novel Sphingolipid-Based Cancer Therapeutics in the Personalized Medicine Era.Advances in cancer research · 2018Review
- The role of G protein-coupled receptors in lymphoid malignancies.Cellular signalling · 2017Review
- Article
- Downstream effects of endocannabinoid on blood cells: implications for health and disease.Cellular and molecular life sciences : CMLS · 2015Review
- Cannabinoid Receptor-2 Regulates Embryonic Hematopoietic Stem Cell Development via Prostaglandin E2 and P-Selectin Activity.Stem cells (Dayton, Ohio) · 2015Article
- Role of Sphingolipids and Metabolizing Enzymes in Hematological Malignancies.Molecules and cells · 2015Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Ceramide levels are elevated in mantle cell lymphoma (MCL) cells following treatment with cannabinoids. Here, we investigated the pathways of ceramide accumulation in the MCL cell line Rec-1 using the stable endocannabinoid analogue R(+)-methanandamide (R-MA). We further interfered with the conversion of ceramide into sphingolipids that promote cell growth. Treatment with R-MA led to increased levels of ceramide species C16, C18, C24, and C(24:1) and transcriptional induction of ceramide synthases (CerS) 3 and 6. The effects were attenuated using SR141716A, which has high affinity to cannabinoid receptor 1 (CB1). The CB1-mediated induction of CerS3 and CerS6 mRNA was confirmed using Win-55,212-2. Simultaneous silencing of CerS3 and CerS6 using small interfering RNA abrogated the R-MA-induced accumulation of C16 and C24. Inhibition of either of the enzymes serine palmitoyl transferase, CerS, and dihydroceramide desaturase within the de novo ceramide pathway reversed ceramide accumulation and cell death induced by R-MA treatment. To enhance the cytotoxic effect R-MA, sphingosine kinase-1 and glucosylceramide synthase, enzymes that convert ceramide to the pro-proliferative sphingolipids sphingosine-1-phospate and glucosylceramide, respectively, were inhibited. Suppression of either enzyme using inhibitors or small interfering RNA potentiated the decreased viability, induction of cell death, and ceramide accumulation induced by R-MA treatment. Our findings suggest that R-MA induces cell death in MCL via CB1-mediated up-regulation of the de novo ceramide synthesis pathway. Furthermore, this is the first study were the cytotoxic effect of a cannabinoid is enhanced by modulation of ceramide metabolism.
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Registered trials
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