ArticleCancer biology & therapy2023
Combination of metformin/efavirenz/fluoxetine exhibits profound anticancer activity via a cancer cell-specific ROS amplification.
Article in Cancer biology & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 17 citations in OpenAlex.
- Mitochondrial Dysfunction at the Crossroads of Necroptosis: Mechanisms, Molecular Mediators, and Therapeutic Opportunities.Journal of cellular and molecular medicine · 2026Review
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- Metformin Suppresses Glioblastoma Tumor Growth and Progression Through the AMPK/FoxO3a/Survivin Axis.Cells · 2026Article
- Mitochondrial DNA mutations and intercellular mitochondrial transfer in cancer: mechanisms, biological effects, and clinical potential.Biomarker research · 2026Review
- Oleanolic acid-chitosan compound inhibits mitochondrial autophagy and malignant transformation of lung cancer through the PTEN/AKT pathway.Turkish journal of medical sciences · 2026Article
- Inhibition of apoptosis in breast cancer cells by si-FoxO3a through the protein digestion and absorption signaling pathway.Oncology letters · 2025Article
- Manganese Superoxide Dismutase: Structure, Function, and Implications in Human Disease.Antioxidants (Basel, Switzerland) · 2025Review
- The Use of Selective Serotonin Reuptake Inhibitor (SSRI) Antidepressants in the Treatment of Lung Cancer.International journal of molecular sciences · 2025Review
- UBC4: A Repurposed Drug Regimen for Adjunctive Use During Bladder Cancer Treatment.Biomedicines · 2025Review
- SBFI-26 enhances apoptosis in docetaxel-treated triple-negative breast cancer cells by increasing ROS levels.BioImpacts : BI · 2025Article
- From antiviral to anticancer: Exploring efavirenz's potential against breast cancer.Indian journal of pharmacology · 2024Article
- Efavirenz: New Hope in Cancer Therapy.Cureus · 2024Review
- Antiretroviral Drugs Impact Autophagy: Opportunities for Drug Repurposing.Frontiers in bioscience (Landmark edition) · 2024Review
- Beyond Psychotropic: Potential Repurposing of Fluoxetine toward Cancer Therapy.International journal of molecular sciences · 2024Review
- Review
- Comparison of Efavirenz and Doravirine Developmental Toxicity in an Embryo Animal Model.International journal of molecular sciences · 2023Article
- Anti-hyperuricemia effect of hesperetin is mediated by inhibiting the activity of xanthine oxidase and promoting excretion of uric acid.Frontiers in pharmacology · 2023Article
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The possible anticancer activity of combination (M + E + F) of metformin (M), efavirenz (E), and fluoxetine (F) was investigated in normal HDF cells and HCT116 human colon cancer cells. Metformin increased cellular FOXO3a, p-FOXO3a, AMPK, p-AMPK, and MnSOD levels in HDFs but not in HCT116 cells. Cellular ATP level was decreased only in HDFs by metformin. Metformin increased ROS level only in HCT116 cells. Transfection of si-FOXO3a into HCT116 reversed the metformin-induced cellular ROS induction, indicating that FOXO3a/MnSOD is the key regulator for cellular ROS level. Viability readout with M, E, and F alone decreased slightly, but the combination of three drugs dramatically decreased cell survival in HCT116, A549, and SK-Hep-1 cancer cells but not in HDF cells. ROS levels in HCT116 cells were massively increased by M + E + F combination, but not in HDF cells. Cell cycle analysis showed that of M + E + F combination caused cell death only in HCT116 cells. The combination of M + E + F reduced synergistically mitochondrial membrane potential and mitochondrial electron transport chain complex I and III activities in HCT116 cells when compared with individual treatments. Western blot analysis indicated that DNA damage, apoptosis, autophagy, and necroptosis-realated factors increased in M + E + F-treated HCT116 cells. Oral administration with M + E + F combination for 3 weeks caused dramatic reductions in tumor volume and weight in HCT116 xenograft model of nude mice when compared with untreated ones. Our results suggest that M + E + F have profound anticancer activity both
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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 Socratic graph.