ArticleInternational journal of molecular medicine2020
Inhibition of autophagy flux by sertraline attenuates TRAIL resistance in lung cancer via death receptor 5 upregulation.
Article in International journal of molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Global research and emerging trends in depression in lung cancer: a bibliometric and visualized study from 2014 to 2024.Frontiers in oncology · 2025Pooled it
- Olanzapine enhances the response of PD-(L)1 inhibitor immunotherapy: A retrospective efficacy analysis in advanced malignancies.iScience · 2026Article
- Repurposing the Antidepressant Sertraline: A Systematic Scoping Review of Its Anticancer Mechanisms.Pharmacology research & perspectives · 2025Article
- Autophagy Modulation by Antidepressants: Mechanisms and Implications.Neurochemical research · 2025Review
- The role of tumor necrosis factor receptor superfamily in cancer: insights into oncogenesis, progression, and therapeutic strategies.NPJ precision oncology · 2025Review
- The Use of Selective Serotonin Reuptake Inhibitor (SSRI) Antidepressants in the Treatment of Lung Cancer.International journal of molecular sciences · 2025Review
- BDNF is a prognostic biomarker involved in the immune infiltration of lung adenocarcinoma and associated with programmed cell death.Oncology letters · 2025Article
- Antidepressant Sertraline Synergistically Enhances Paclitaxel Efficacy by Inducing Autophagy in Colorectal Cancer Cells.Molecules (Basel, Switzerland) · 2024Article
- 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
- Serotonin signalling in cancer: Emerging mechanisms and therapeutic opportunities.Clinical and translational medicine · 2024Review
- Antidepressants as Autophagy Modulators for Cancer Therapy.Molecules (Basel, Switzerland) · 2023Review
- An Antidepressant Drug Increased TRAIL Receptor-2 Expression and Sensitized Lung Cancer Cells to TRAIL-induced Apoptosis.Anti-cancer agents in medicinal chemistry · 2023Article
- Repurposed Drugs in Gastric Cancer.Molecules (Basel, Switzerland) · 2022Review
- Antidepressant Drug Sertraline against Human Cancer Cells.Biomolecules · 2022Review
- Repurposing autophagy regulators in brain tumors.International journal of cancer · 2022Review
- Effects of sertraline and sorafenib on HepG2 cells with a possible link to autophagy.Medicine internationalArticle
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL) is a potential target for cancer therapy, owing to its ability to selectively kill cancer cells without causing significant toxicity to normal cells. However, due to the lack of death receptor expression, cancer cells can become highly resistant to TRAIL. Hence, it is vital to develop agents that restore TRAIL efficacy. Sertraline is an antidepressant drug with anticancer properties. To the best of our knowledge, this is the first study to demonstrate that sertraline inhibits autophagic flux and increases the expression of death receptor 5 (DR5) on TRAIL‑resistant lung cancer cells. Inhibition of autophagy using autophagy inhibitors 3‑methyladenine and chloroquine upregulated the expression of DR5 and enhanced TRAIL‑induced apoptosis, as confirmed by the increase of pro‑apoptotic proteins caspase‑8 and caspase‑3. Silencing DR5 expression using DR5 small interfering RNA prevented sertraline‑induced TRAIL‑mediated apoptosis, indicating the role of DR5 in TRAIL‑mediated apoptosis. Overall, sertraline enhanced TRAIL‑mediated apoptosis via the downregulation of AMP‑activated protein kinase phosphorylation, resulting in the inhibition of autophagic flux, upregulation of DR5 expression, and activation of the apoptotic caspase cascade. These data suggested that sertraline could be used to sensitize human lung cancer cells to TRAIL, while also serving as a therapeutic option in cancer patients with depression.
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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.