ArticleJournal of pineal research2015
Ceramide metabolism regulates autophagy and apoptotic cell death induced by melatonin in liver cancer cells.
Article in Journal of pineal research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Application of lipidomics strategy to explore aging-related biomarkers and potential anti-aging mechanisms of ginseng.Biogerontology · 2021Trial
- Deconstructing the RAGE signaling maze: the molecular key to opening a new dimension of ovarian anti-aging.Experimental & molecular medicine · 2026Review
- Decoding autophagy in neuro-tumor crosstalk: from underlying mechanisms to translational opportunities.Theranostics · 2026Review
- Pinealectomy-Induced Melatonin Deficiency Exerts Age-Specific Effects on Sphingolipid Turnover in Rats.International journal of molecular sciences · 2025Article
- Melatonin: a natural guardian in cancer treatment.Frontiers in pharmacology · 2025Review
- Programmed cell death and melatonin: A comprehensive review.Functional & integrative genomics · 2024Review
- Melatonin attenuates scopolamine-induced cognitive dysfunction through SIRT1/IRE1α/XBP1 pathway.CNS neuroscience & therapeutics · 2024Article
- Anti-drug resistance, anti-inflammation, and anti-proliferation activities mediated by melatonin in doxorubicin-resistant hepatocellular carcinoma: in vitro investigations.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Nonalcoholic steatohepatitis critically rewires the ischemia/reperfusion-induced dysregulation of cardiolipins and sphingolipids in mice.Hepatobiliary surgery and nutrition · 2023Article
- Melatonin and 5-fluorouracil combination chemotherapy: opportunities and efficacy in cancer therapy.Cell communication and signaling : CCS · 2023Review
- Dual anti-angiogenic and anti-metastatic activity of myriocin synergistically enhances the anti-tumor activity of cisplatin.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- Insights into the roles and pathomechanisms of ceramide and sphigosine-1-phosphate in nonalcoholic fatty liver disease.International journal of biological sciences · 2023Review
- Mysterious sphingolipids: metabolic interrelationships at the center of pathophysiology.Frontiers in physiology · 2023Review
- Prognostic signatures of sphingolipids: Understanding the immune landscape and predictive role in immunotherapy response and outcomes of hepatocellular carcinoma.Frontiers in immunology · 2023Article
- Machine learning-enhanced insights into sphingolipid-based prognostication: revealing the immunological landscape and predictive proficiency for immunomotherapy and chemotherapy responses in pancreatic carcinoma.Frontiers in molecular biosciences · 2023Article
- Inhibition of sphingolipid metabolism in osteosarcoma protects against CD151-mediated tumorigenicity.Cell & bioscience · 2022Article
- Comparative Analysis of the Cytotoxic Effect of a Complex of Selenium Nanoparticles Doped with Sorafenib, "Naked" Selenium Nanoparticles, and Sorafenib on Human Hepatocyte Carcinoma HepG2 Cells.International journal of molecular sciences · 2022Article
- Melatonin Alleviates Liver Fibrosis by Inhibiting Autophagy.Current medical science · 2022Article
- Serine palmitoyltransferase long chain subunit 3 is associated with hepatocellular carcinoma in patients with NAFLD.Molecular and clinical oncology · 2022Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Autophagy is a process that maintains homeostasis during stress, although it also contributes to cell death under specific contexts. Ceramides have emerged as important effectors in the regulation of autophagy, mediating the crosstalk with apoptosis. Melatonin induces apoptosis of cancer cells; however, its role in autophagy and ceramide metabolism has yet to be clearly elucidated. This study was aimed to evaluate the effect of melatonin administration on autophagy and ceramide metabolism and its possible link with melatonin-induced apoptotic cell death in hepatocarcinoma (HCC) cells. Melatonin (2 mm) transiently induced autophagy in HepG2 cells through JNK phosphorylation, characterized by increased Beclin-1 expression, p62 degradation, and LC3II and LAMP-2 colocalization, which translated in decreased cell viability. Moreover, ATG5 silencing sensitized HepG2 cells to melatonin-induced apoptosis, suggesting a dual role of autophagy in cell death. Melatonin enhanced ceramide levels through both de novo synthesis and acid sphingomyelinase (ASMase) stimulation. Serine palmitoyltransferase (SPT) inhibition with myriocin prevented melatonin-induced autophagy and ASMase inhibition with imipramine-impaired autophagy flux. However, ASMase inhibition partially protected HepG2 cells against melatonin, while SPT inhibition significantly enhanced cell death. Findings suggest a crosstalk between SPT-mediated ceramide generation and autophagy in protecting against melatonin, while specific ASMase-induced ceramide production participates in melatonin-mediated cell death. Thus, dual blocking of SPT and autophagy emerges as a potential strategy to potentiate the apoptotic effects of melatonin in liver cancer cells.
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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.