ArticleOncotarget2017
The antidepressant fluoxetine induces necrosis by energy depletion and mitochondrial calcium overload.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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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
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Who cites it
24 citing papers in PubMed, 49 citations in OpenAlex.
- Article
- Fluoxetine Mitigates Human Sperm Quality by Disrupting the Antioxidant Defense System and Altering the Expression of Apoptosis-Related Genes: An In Vitro Study.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Beyond Psychotropic: Potential Repurposing of Fluoxetine toward Cancer Therapy.International journal of molecular sciences · 2024Review
- Binary effects of fluoxetine and zinc on the biomarker responses of the non-target model organism Daphnia magna.Environmental science and pollution research international · 2024Article
- Upregulation of S100A8 in peripheral blood mononuclear cells from patients with depression treated with SSRIs: a pilot study.Proteome science · 2023Article
- Therapeutic Potential of the Purinergic System in Major Depressive Disorder Associated with COVID-19.Cellular and molecular neurobiology · 2023Review
- Repurposing Antidepressants and Phenothiazine Antipsychotics as Efflux Pump Inhibitors in Cancer and Infectious Diseases.Antibiotics (Basel, Switzerland) · 2023Review
- Integrating cell morphology with gene expression and chemical structure to aid mitochondrial toxicity detection.Communications biology · 2022Article
- Mitochondrial adaptation in cancer drug resistance: prevalence, mechanisms, and management.Journal of hematology & oncology · 2022Review
- Prescription drugs and mitochondrial metabolism.Bioscience reports · 2022Review
- Related Fluoxetine and Methylprednisolone Changes of TNF-α and IL-6 Expression in The Hypothyroidism Rat Model of Spinal Cord Injury.Cell journal · 2021Article
- Molecular Consequences of Depression Treatment: A Potential In Vitro Mechanism for Antidepressants-Induced Reprotoxic Side Effects.International journal of molecular sciences · 2021Article
- Fluoxetine affects cytosolic cAMP, ATP, CaThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2021Article
- Modifications of Plasma Membrane Organization in Cancer Cells for Targeted Therapy.Molecules (Basel, Switzerland) · 2021Review
- Methiothepin Suppresses Human Ovarian Cancer Cell Growth by Repressing Mitochondrion-Mediated Metabolism and Inhibiting Angiogenesis In Vivo.Pharmaceutics · 2020Article
- Apoptotic effect of fluoxetine through the endoplasmic reticulum stress pathway in the human gastric cancer cell line AGS.Naunyn-Schmiedeberg's archives of pharmacology · 2020Article
- Fluoxetine Simultaneously Induces Both Apoptosis and Autophagy in Human Gastric Adenocarcinoma Cells.Biomolecules & therapeutics · 2020Article
- Neuronal life or death linked to depression treatment: the interplay between drugs and their stress-related outcomes relate to single or combined drug therapies.Apoptosis : an international journal on programmed cell death · 2019Article
- Inhibition by fluoxetine of LH-stimulated cyclic AMP synthesis in tumor Leydig cells partly involves AMPK activation.PloS one · 2019Article
- Revisiting the Crabtree/Warburg effect in a dynamic perspective: a fitness advantage against sugar-induced cell death.Cell cycle (Georgetown, Tex.) · 2018Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Selective Serotonin Reuptake Inhibitor antidepressants, such as fluoxetine (Prozac), have been shown to induce cell death in cancer cells, paving the way for their potential use as cancer therapy. These compounds are able to increase cytosolic calcium concentration ([Ca2+]cyt), but the involved mechanisms and their physiological consequences are still not well understood. Here, we show that fluoxetine induces an increase in [Ca2+]cyt by emptying the endoplasmic reticulum (ER) through the translocon, an ER Ca2+ leakage structure. Our data also show that fluoxetine inhibits oxygen consumption and lowers mitochondrial ATP. This latter is essential for Ca2+ reuptake into the ER, and we postulated therefore that the fluoxetine-induced decrease in mitochondrial ATP production results in the emptying of the ER, leading to capacitative calcium entry. Furthermore, Ca2+ quickly accumulated in the mitochondria, leading to mitochondrial Ca2+ overload and cell death. We found that fluoxetine could induce an early necrosis in human peripheral blood lymphocytes and Jurkat cells, and could also induce late apoptosis, especially in the tumor cell line. These results shed light on fluoxetine-induced cell death and its potential use in cancer treatment.
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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.