ArticleToxicological sciences : an official journal of the Society of Toxicology2014
Sertraline, an antidepressant, induces apoptosis in hepatic cells through the mitogen-activated protein kinase pathway.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2014. 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, 71 citations in OpenAlex.
- Selective serotonin reuptake inhibitor use and the risk of hepatocellular carcinoma: a systematic review and dose-response analysis of cohort studies with one million participants.European journal of clinical pharmacology · 2022Pooled it
- Antidepressant Use and Mortality Among Patients With Hepatocellular Carcinoma.JAMA network open · 2023Trial
- Investigation of the modulatory effects of fabomotizole and/or sertraline on cisplatin nephrotoxicity via in vivo and in vitro approaches: insights into the role of Sig-1R/ERK1/2 signaling in regulating mitochondrial dynamics and apoptotic cellular death.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- MAP4Ks drive cell death in response tomBio · 2026Article
- Folic acid attenuates maternal sertraline-induced hepatic injury in rat offspring.Scientific reports · 2026Article
- Role of central and peripheral serotonin in liver physiology and diseases.Theranostics · 2026Review
- An Overview of the Potential Use of Selective Serotonin Reuptake Inhibitors (SSRIs) in Cancer Treatment.Current cancer drug targets · 2026Review
- Repurposing the Antidepressant Sertraline: A Systematic Scoping Review of Its Anticancer Mechanisms.Pharmacology research & perspectives · 2025Article
- Unraveling the Anticancer Potential of SSRIs in Prostate Cancer by Combining Computational Systems Biology andACS omega · 2025Article
- Folic Acid Mitigates Sertraline-Induced Liver Damage in Adult Female Albino Rats During Pregnancy and Postpartum: A Biochemical and Histological Study.Medicina (Kaunas, Lithuania) · 2025Article
- Roles of X-box binding protein 1 in liver pathogenesis.Clinical and molecular hepatology · 2025Review
- Antidepressant Sertraline Synergistically Enhances Paclitaxel Efficacy by Inducing Autophagy in Colorectal Cancer Cells.Molecules (Basel, Switzerland) · 2024Article
- Serotonin signalling in cancer: Emerging mechanisms and therapeutic opportunities.Clinical and translational medicine · 2024Review
- Modulation of ACE2/Ang1-7/Mas and ACE/AngII/AT1 axes affects anticancer properties of sertraline in MCF-7 breast cancer cells.Biochemistry and biophysics reports · 2024Article
- The janus face of serotonin: Regenerative promoter and chronic liver disease aggravator.Heliyon · 2024Review
- Evaluation on the Potential for Hepatotoxic Components from Herba Epimedii to Induce Apoptosis in HepG2 Cells and the Analysis of the Influence of Metabolism in Liver Microsomes.Molecules (Basel, Switzerland) · 2024Article
- Sertraline induced acute hepatocellular liver injury in patient with major depressive disorder: a case report.Frontiers in psychiatry · 2024Article
- Antidepressant Sertraline Hydrochloride Inhibits the Growth of HER2+ AU565 Breast Cancer Cell Line through Induction of Apoptosis and Cell Cycle Arrest.Anti-cancer agents in medicinal chemistry · 2024Article
- Study of the roles of cytochrome P450 (CYPs) in the metabolism and cytotoxicity of perhexiline.Archives of toxicology · 2022Article
- Antidepressant Drug Sertraline against Human Cancer Cells.Biomolecules · 2022Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Sertraline is generally used for the treatment of depression and is also approved for the treatment of panic, obsessive-compulsive, and posttraumatic stress disorders. Previously, using rat primary hepatocytes and isolated mitochondria, we demonstrated that sertraline caused hepatic cytotoxicity and mitochondrial impairment. In the current study, we investigated and characterized molecular mechanisms of sertraline toxicity in human hepatoma HepG2 cells. Sertraline decreased cell viability and induced apoptosis in a dose- and time-dependent manner. Sertraline activated the intrinsic checkpoint protein caspase-9 and caused the release of cytochrome c from mitochondria to cytosol; this process was Bcl-2 family dependent because antiapoptotic Bcl-2 family proteins were decreased. Pretreatment of the HepG2 cells with caspase-3, caspase-8, and caspase-9 inhibitors partially but significantly reduced the release of lactate dehydrogenase, indicating that sertraline-induced apoptosis is mediated by both intrinsic and extrinsic apoptotic pathways. Moreover, sertraline markedly increased the expression of tumor necrosis factor (TNF) and the phosphorylation of JNK, extracellular signal-regulated kinase (ERK1/2), and p38. In sertraline-treated cells, the induction of apoptosis and cell death was shown to be the result of activation of JNK, but not ERK1/2 or p38 in the mitogen-activated protein kinase (MAPK) pathway. Furthermore, silencing MAP4K4, the upstream kinase of JNK, attenuated both apoptosis and cell death caused by sertraline. Taken together, our findings suggest that sertraline induced apoptosis in HepG2 cells at least partially via activation of the TNF-MAP4K4-JNK cascade signaling pathway.
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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.