ArticleOncotarget2017
Roflumilast restores cAMP/PKA/CREB signaling axis for FtMt-mediated tumor inhibition of ovarian cancer.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 45 citations in OpenAlex.
- The regulation of mitochondrial ferritin on mitochondrial redox balance is essential to cell fate decision.Redox biology · 2026Review
- Clinical and Functional Characterization of PDE1A as a Wnt/Oncology research · 2026Article
- Cellular cAMP Content and Mitochondrial Profile Define Different Subtypes of Ovarian Cancer Cells.International journal of molecular sciences · 2025Article
- Butyrate enhances gut dysbiosis by activating the cAMP/PKA/CREB signaling pathway to inhibit the progression of endometrial carcinoma.BMC microbiology · 2025Article
- PKIB facilitates bladder cancer proliferation and metastasis through mediation of HSP27 phosphorylation by PKA.Cell death & disease · 2025Article
- Bilirubin metabolism in relation to cancer.Frontiers in oncology · 2025Review
- The multifaceted role of phosphodiesterase 4 in tumor: from tumorigenesis to immunotherapy.Frontiers in immunology · 2025Review
- Roflumilast inhibits tumor growth and migration in STK11/LKB1 deficient pancreatic cancer.Cell death discovery · 2024Article
- Unleashing T cell anti-tumor immunity: new potential for 5-Nonloxytryptamine as an agent mediating MHC-I upregulation in tumors.Molecular cancer · 2023Article
- A novel view of ferritin in cancer.Biochimica et biophysica acta. Reviews on cancer · 2023Review
- Ovarian Cancer: A Landscape of Mitochondria with Emphasis on Mitochondrial Dynamics.International journal of molecular sciences · 2023Review
- Detection of Ferroptosis by Immunohistochemistry and Immunofluorescence.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Article
- cAMP-Dependent Signaling and Ovarian Cancer.Cells · 2022Review
- Phosphodiesterase 10A (PDE10A) as a novel target to suppress β-catenin and RAS signaling in epithelial ovarian cancer.Journal of ovarian research · 2022Article
- The Complexity and Multiplicity of the Specific cAMP Phosphodiesterase Family: PDE4, Open New Adapted Therapeutic Approaches.International journal of molecular sciences · 2022Review
- Review
- Review
- Gene-environment interaction with smoking for increased non-muscle-invasive bladder cancer tumor size.Translational andrology and urology · 2020Article
- Glucocorticoid Receptor α Mediates Roflumilast's Ability to Restore Dexamethasone Sensitivity in COPD.International journal of chronic obstructive pulmonary disease · 2020Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The abrogation of cAMP generation by overexpression of PDE isoforms promotes the inflammatory pathology, and the PDE inhibitors have showed the potential anti-inflammation effects in clinical. However, the function of PDE inhibitors in cancer treatment remains unclear. We here investigated the role of PDE4 inhibitor Roflumilast in the treatment of ovarian cancer. We found that Roflumilast could effectively inhibit the proliferation, and induce apoptosis and cell cycle arrest in two ovarian cancer cell lines OVCAR3 and SKOV3. Meanwhile, the cAMP/PKA/CREB signals was activated by Roflumilast, which was accompanied by the up-regulation of mitochondrial ferritin (FtMt) level. Interestingly, forced expression of FtMt in ovarian cancer enhanced the apoptosis and inhibited tumor growth and the PKA inhibitor H89 and knockdown of CREB significantly repressed the expression of FtMt to restore the tumor proliferation and inhibit apoptosis. In addition, we found that Roflumilast-induced phosphorylated CREB directly promoted transcription of FtMt, indicating that Roflumilast up-regulated the expression of FtMt in ovarian cancer via cAMP/PKA/CREB signals. The anti-tumor role of Roflumilast
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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 OpenQuestion graph.