ArticlePloS one2013
Inhibition of oxidative stress-elicited AKT activation facilitates PPARγ agonist-mediated inhibition of stem cell character and tumor growth of liver cancer cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 33 citations in OpenAlex.
- Analysis and validation of abnormal signaling pathways and immune cell infiltration characteristics in digestive system cancers based on peroxisome-related genes.Biology direct · 2026Article
- Dynamic interplay of nuclear receptors in tumor cell plasticity and drug resistance: Shifting gears in malignant transformations and applications in cancer therapeutics.Cancer metastasis reviews · 2024Review
- The Association between NADPH Oxidase 2 (NOX2) and Drug Resistance in Cancer.Current cancer drug targets · 2024Review
- The role of peroxisome proliferator-activated receptors in the tumor microenvironment, tumor cell metabolism, and anticancer therapy.Frontiers in pharmacology · 2023Review
- Signaling pathways in the regulation of cancer stem cells and associated targeted therapy.MedComm · 2022Review
- Renal Cell Cancer and Obesity.International journal of molecular sciences · 2022Review
- Targeting Breast Cancer and Their Stem Cell Population through AMPK Activation: Novel Insights.Cells · 2022Review
- NADPH Oxidases: Redox Regulators of Stem Cell Fate and Function.Antioxidants (Basel, Switzerland) · 2021Review
- Review
- Targeting cancer stem cell pathways for cancer therapy.Signal transduction and targeted therapy · 2020Review
- Aloin Inhibits the Proliferation and Migration of Gastric Cancer Cells by Regulating NOX2-ROS-Mediated Pro-Survival Signal Pathways.Drug design, development and therapy · 2020Article
- Curcumin: a therapeutic strategy in cancers by inhibiting the canonical WNT/β-catenin pathway.Journal of experimental & clinical cancer research : CR · 2019Review
- Review
- The Akt/mTOR pathway in cancer stem/progenitor cells is a potential therapeutic target for glioblastoma and neuroblastoma.Oncotarget · 2018Article
- Crosstalk Between Peroxisome Proliferator-Activated Receptor Gamma and the Canonical WNT/β-Catenin Pathway in Chronic Inflammation and Oxidative Stress During Carcinogenesis.Frontiers in immunology · 2018Review
- 15d-PGJ2 is a new hope for controlling tumor growth.American journal of translational research · 2018Review
- PPAR-γ Agonists As Antineoplastic Agents in Cancers with Dysregulated IGF Axis.Frontiers in endocrinology · 2017Review
- Peroxisome proliferator-activated receptor-γ agonist troglitazone suppresses transforming growth factor-β1 signalling through miR-92b upregulation-inhibited Axl expression in human keloid fibroblasts in vitro.American journal of translational research · 2016Article
- Insights into the Role and Interdependence of Oxidative Stress and Inflammation in Liver Diseases.Oxidative medicine and cellular longevity · 2016Review
- A multi-targeted approach to suppress tumor-promoting inflammation.Seminars in cancer biology · 2015Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Emerging evidence suggests that tumor-initiating cells (TICs) are the most malignant cell subpopulation in tumors because of their resistance to chemotherapy or radiation treatment. Targeting TICs may be a key innovation for cancer treatment. In this study, we found that PPARγ agonists inhibited the cancer stem cell-like phenotype and attenuated tumor growth of human hepatocellular carcinoma (HCC) cells. Reactive oxygen species (ROS) initiated by NOX2 upregulation were partially responsible for the inhibitory effects mediated by PPARγ agonists. However, PPARγ agonist-mediated ROS production significantly activated AKT, which in turn promoted TIC survival by limiting ROS generation. Inhibition of AKT, by either pharmacological inhibitors or AKT siRNA, significantly enhanced PPARγ agonist-mediated inhibition of cell proliferation and stem cell-like properties in HCC cells. Importantly, in nude mice inoculated with HCC Huh7 cells, we demonstrated a synergistic inhibitory effect of the PPARγ agonist rosiglitazone and the AKT inhibitor triciribine on tumor growth. In conclusion, we observed a negative feedback loop between oxidative stress and AKT hyperactivation in PPARγ agonist-mediated suppressive effects on HCCs. Combinatory application of an AKT inhibitor and a PPARγ agonist may provide a new strategy for inhibition of stem cell-like properties in HCCs and treatment of liver cancer.
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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.