ArticleBiochemical pharmacology2016
Activation of the MAPK/Akt/Nrf2-Egr1/HO-1-GCLc axis protects MG-63 osteosarcoma cells against 15d-PGJ2-mediated cell death.
Article in Biochemical pharmacology, 2016. 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, 38 citations in OpenAlex.
- PPARγ Signaling in the Central Nervous System: A Review of the Implications in Synaptic Plasticity, Neuroinflammatory and Neoplastic Processes.Neurochemical research · 2026Review
- Nrf2: A key regulator in chemoradiotherapy resistance of osteosarcoma.Genes & diseases · 2025Review
- Durvalumab and T-DXd Synergistically Promote Apoptosis of Cholangiocarcinoma Cells by Downregulating EGR1 Expression Through Inhibiting P38 MAPK Pathway.Applied biochemistry and biotechnology · 2025Article
- Glutathione-Dependent Pathways in Cancer Cells.International journal of molecular sciences · 2024Review
- Review
- Lipid Peroxidation-Related Redox Signaling in Osteosarcoma.International journal of molecular sciences · 2024Review
- Harnessing peroxisome proliferator-activated receptor γ agonists to induce Heme Oxygenase-1: a promising approach for pulmonary inflammatory disorders.Cell communication and signaling : CCS · 2024Review
- Transcriptome Profiling of Cardiac Glycoside Treatment Reveals EGR1 and Downstream Proteins of MAPK/ERK Signaling Pathway in Human Breast Cancer Cells.International journal of molecular sciences · 2023Article
- The prognostic and therapeutic potential of HO-1 in leukemia and MDS.Cell communication and signaling : CCS · 2023Review
- Induction of Heme Oxygenase-1 by 15d-Prostaglandin JAntioxidants (Basel, Switzerland) · 2022Article
- Empagliflozin activates Sestrin2-mediated AMPK/mTOR pathway and ameliorates lipid accumulation in obesity-related nonalcoholic fatty liver disease.Frontiers in pharmacology · 2022Article
- 15d-PGJInternational journal of molecular sciences · 2021Article
- Protective Effects of Maclurin against Benzo[a]pyrene via Aryl Hydrocarbon Receptor and Nuclear Factor Erythroid 2-Related Factor 2 Targeting.Antioxidants (Basel, Switzerland) · 2021Article
- Role of TGF-β in pancreatic ductal adenocarcinoma progression and PD-L1 expression.Cellular oncology (Dordrecht, Netherlands) · 2021Article
- Article
- Article
- Oct4 upregulates osteopontin via Egr1 and is associated with poor outcome in human lung cancer.BMC cancer · 2019Article
- Identification of Differentially Expressed Genes under the Regulation of Transcription Factors in Osteosarcoma.Pathology oncology research : POR · 2019Article
- Haem oxygenase-1 up-regulation by rosiglitazone via ROS-dependent Nrf2-antioxidant response elements axis or PPARγ attenuates LPS-mediated lung inflammation.British journal of pharmacology · 2018Article
- The metal-nonoate Ni(SalPipNONO) inhibitsOncotarget · 2018Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Despite considerable efforts to improve treatment modalities for osteosarcoma (OS), patient survival remains poor mainly due to pro-survival pathways in OS cells. Among others, prostaglandins (PGs) are the potent regulators of bone homoeostasis and OS pathophysiology. Therefore, the present study aimed to elucidate the impact of 15-deoxy-Δ(12,14)-PGJ2 (15d-PGJ2, a stable PGD2 degradation product) on cell death/cell survival pathways in p53-deficient MG-63 OS cells. Our findings show that 15d-PGJ2 induces generation of reactive oxygen species that promote p38 MAPK activation and subsequent Akt phosphorylation. This pathway induced nuclear expression of Nrf2 and Egr1, and increased transcription of haem oxygenase-1 (HO-1) and the catalytic subunit of glutamate cysteine ligase (GCLc), catalysing the first step in GSH synthesis. Silencing of Nrf2, Egr1 and HO-1 significantly elevated 15d-PGJ2-mediated reduction of cellular metabolic activity. Activation of cell survival genes including HO-1 and GCLc inhibited 15d-PGJ2-induced cleavage of pro-caspase-3 and PARP. Annexin V/propidium iodide staining showed an increase in early/late apoptotic cells in response to 15d-PGJ2. The observed 15d-PGJ2-mediated signalling events are independent of PGD2 receptors (DP1 and DP2) and PPARγ. In addition, the electrophilic carbon atom C9 is a prerequisite for the observed activity of 15d-PGJ2. The present data show that the intracellular redox imbalance acted as a node and triggered both death and survival pathways in response to 15d-PGJ2. Pharmacological or genetic interference of the pro-survival pathway, the p38 MAPK/Akt/Nrf2-Egr1/HO-1-GCLc axis, sensitizes MG-63 cells towards 15d-PGJ2-mediated apoptosis.
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