ArticlePloS one2015
Melatonin Activates Endoplasmic Reticulum Stress and Apoptosis in Rats with Diethylnitrosamine-Induced Hepatocarcinogenesis.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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
41 citing papers in PubMed, 84 citations in OpenAlex.
- Regulation of Endoplasmic Reticulum Stress Suppresses Early Pro-Tumorigenic Events During N-Nitrosodiethylamine-Induced Hepatocarcinogenesis.Journal of biochemical and molecular toxicology · 2026Article
- Hepatocellular Carcinoma Around the Clock.Current oncology (Toronto, Ont.) · 2026Review
- Therapeutic Potential of Melatonin in Gastrointestinal Cancers: Molecular Mechanisms, Preclinical Evidence and Clinical Implications.Journal of pineal research · 2026Review
- Melatonin Ameliorates Isoproterenol-Induced Cardiac Fibrosis by Suppressing BIP/PERK/CHOP Signaling Pathways; Insights from In Silico and In vivo Studies.Cell biochemistry and biophysics · 2025Article
- Melatonin Induces PERK-ATF4 Unfolded Protein Response and Apoptosis in Human Choriocarcinoma Cells.Journal of pineal research · 2025Article
- Night shift-induced circadian disruption: links to initiation of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and risk of hepatic cancer.Hepatoma research · 2024Article
- Circadian rhythms and inflammatory diseases of the liver and gut.Liver research (Beijing, China) · 2023Review
- 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
- The apoptotic effects of soybean agglutinin were induced through three different signal pathways by down-regulating cytoskeleton proteins in IPEC-J2 cells.Scientific reports · 2023Article
- A novel mechanistic approach for the anti-fibrotic potential of rupatadine in rat liver via amendment of PAF/NF-ĸB p65/TGF-β1 and hedgehog/HIF-1α/VEGF trajectories.Inflammopharmacology · 2023Article
- Honey: A Promising Therapeutic Supplement for the Prevention and Management of Osteoporosis and Breast Cancer.Antioxidants (Basel, Switzerland) · 2023Review
- Melatonin Attenuates Inflammation, Oxidative Stress, and DNA Damage in Mice with Nonalcoholic Steatohepatitis Induced by a Methionine- and Choline-Deficient Diet.Inflammation · 2022Article
- Melatonin drives apoptosis in head and neck cancer by increasing mitochondrial ROS generated via reverse electron transport.Journal of pineal research · 2022Article
- Understanding the Mechanism of Action of Melatonin, Which Induces ROS Production in Cancer Cells.Antioxidants (Basel, Switzerland) · 2022Review
- Isatin Counteracts Diethylnitrosamine/2-Acetylaminofluorene-Induced Hepatocarcinogenesis in Male Wistar Rats by Upregulating Anti-Inflammatory, Antioxidant, and Detoxification Pathways.Antioxidants (Basel, Switzerland) · 2022Article
- Melatonin prevents oxidative stress, inflammatory activity, and DNA damage in cirrhotic rats.World journal of gastroenterology · 2022Article
- The Pathogenesis of HCC Driven by NASH and the Preventive and Therapeutic Effects of Natural Products.Frontiers in pharmacology · 2022Review
- Ameliorative potential of manganese nanoparticles with low-level ionizing radiation against experimentally induced hepatocarcinogenesis.Environmental science and pollution research international · 2021Article
- Se-Methylselenocysteine Alleviates Liver Injury in Diethylnitrosamine (DEN)-Induced Hepatocellular Carcinoma Rat Model by Reducing Liver Enzymes, Inhibiting Angiogenesis, and Suppressing Nitric Oxide (NO)/Nitric Oxide Synthase (NOS) Signaling Pathway.Medical science monitor : international medical journal of experimental and clinical research · 2021Article
- Endoplasmic Reticulum Stress and Autophagy in the Pathogenesis of Non-alcoholic Fatty Liver Disease (NAFLD): Current Evidence and Perspectives.Current obesity reports · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) is one of the most lethal human cancers worldwide because of its high incidence, its metastatic potential and the low efficacy of conventional treatment. Inactivation of apoptosis is implicated in tumour progression and chemotherapy resistance, and has been linked to the presence of endoplasmic reticulum stress. Melatonin, the main product of the pineal gland, exerts anti-proliferative, pro-apoptotic and anti-angiogenic effects in HCC cells, but these effects still need to be confirmed in animal models. Male Wistar rats in treatment groups received diethylnitrosamine (DEN) 50 mg/kg intraperitoneally twice/once a week for 18 weeks. Melatonin was given in drinking water at 1 mg/kg/d, beginning 5 or 12 weeks after the start of DEN administration. Melatonin improved survival rates and successfully attenuated liver injury, as shown by histopathology, decreased levels of serum transaminases and reduced expression of placental glutathione S-transferase. Furthermore, melatonin treatment resulted in a significant increase of caspase 3, 8 and 9 activities, polyadenosine diphosphate (ADP) ribose polymerase (PARP) cleavage, and Bcl-associated X protein (Bax)/Bcl-2 ratio. Cytochrome c, p53 and Fas-L protein concentration were also significantly enhanced by melatonin. Melatonin induced an increased expression of activating transcription factor 6 (ATF6), C/EBP-homologous protein (CHOP) and immunoglobulin heavy chain-binding protein (BiP), while cyclooxygenase (COX)-2 expression decreased. Data obtained suggest that induction of apoptosis and ER stress contribute to the beneficial effects of melatonin in rats with DEN-induced HCC.
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.