ArticleOncoTargets and therapy2019
Methotrexate-induced apoptosis in human ovarian adenocarcinoma SKOV-3 cells via ROS-mediated bax/bcl-2-cyt-c release cascading.
Article in OncoTargets and therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 53 citations in OpenAlex.
- Methotrexate Alters Nrf2/HO-1 Protein Expression and Intrinsic Apoptosis-Associated Protein Responses in OVCAR-3 Ovarian Cancer Cells: Differential Modulation by Antioxidant Compounds.Journal of biochemical and molecular toxicology · 2026Article
- Cellular Anti-Apoptotic Effects of Dapagliflozin in Methotrexate-Induced Liver Toxicity: Bax/Bcl-2/Cyt-C/Cas-9/Cas-3 Signaling Pathway.International journal of molecular sciences · 2026Article
- Protodioscin enhances Methotrexate-induced senescence and senolytic activity in HepG2 liver cancer spheroids by modulating cell cycle regulators and the TGF-β/p-Smad2-4 signaling pathway.Scientific reports · 2025Article
- Diversity of oxidative stress and senescence phenotypes induced by chemotherapeutic agents in HUVECs.Scientific reports · 2025Article
- Oxidative Stress and Inflammation: Drivers of Tumorigenesis and Therapeutic Opportunities.Antioxidants (Basel, Switzerland) · 2025Review
- A methotrexate labelled dual metal oxide nanocomposite for long-lasting anti-cancer theranostics.Materials today. Bio · 2025Article
- Review
- Chemical Composition, In Vitro Antitumor Effect, and Toxicity in Zebrafish of the Essential Oil fromBiomolecules · 2023Article
- In vitro hepatotoxicity evaluation of methotrexate-loaded niosome formulation: fabrication, characterization and cell culture studies.Turkish journal of medical sciences · 2023Article
- Synthesis of Zeolitic imidazolate frameworks-8@ layered double hydroxide polyhedral nanocomposite with designed porous voids as an effective carrier for anti-cancer drug-controlled delivery.IET nanobiotechnology · 2023Article
- Targeting purine metabolism in ovarian cancer.Journal of ovarian research · 2022Review
- Photoactivation of Chemotherapeutic Agents with Cerenkov Radiation for Chemo-Photodynamic Therapy.ACS omega · 2022Article
- Mitochondria preserve an autarkic one-carbon cycle to confer growth-independent cancer cell migration and metastasis.Nature communications · 2022Article
- Activation of RSK2 upregulates SOX8 to promote methotrexate resistance in gestational trophoblastic neoplasia.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- Study on the effects of the different polar group of EPA-enriched phospholipids on the proliferation and apoptosis in 95D cells.Marine life science & technology · 2021Article
- Daphnoretin induces reactive oxygen species-mediated apoptosis in melanoma cells.Oncology letters · 2021Article
- Fabrication of methotrexate-loaded gold nanoconjugates and its enhanced anticancer activity in breast cancer.3 Biotech · 2021Article
- Insights into the Role of Oxidative Stress in Ovarian Cancer.Oxidative medicine and cellular longevity · 2021Review
- Active Monomer RTR-1 Derived from the Root ofCancer management and research · 2020Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionThe communication between a substance and a cell may depend on whether the cell is normal or pathological. The disease cells and drug interaction may occasionally overcome beneficial action of the drug; subsequently, it is important to investigate the effect of the drug in both the normal and target cells. This study aimed to evaluate the methotrexate (MTX) antiproliferative effect and explore the mechanistic approach to investigate the cell death index in SKOV-3 ovarian cells during treatment with MTX.
methodsIn vitro studies of SKOV-3 cells were examined by tetrazolium assay after exposure to various concentrations of MTX. Moreover, reactive oxygen species (ROS) generation, mitochondrial membrane potential, DNA damage, and AO/EtBr staining morphological analysis of necrotic/apoptotic cells were detected; cellular impairment in mitochondria and DNA was confirmed by JC-1 mitotracker/DAPI, respectively, and cell death pathway markers; bax/bcl-2 were analyzed.
resultsA dose-dependent antiproliferative effect of MTX treatment was observed in SKOV-3 cells; the prominent inhibitory concentration was 40 µM of MTX (
conclusionOur findings suggest that MTX acts on SKOV-3 cancer cells by increasing intracellular ROS levels, leading to DNA damage and altering the MMP along with apoptotic gene upregulation. This mechanism may provide new therapeutic targets to improve tumor treatment.
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