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From hormonal immunomodulation to glioblastoma therapy: the emerging role of Ouabain
Arthur Gomes de Andrade1, Deyse Cristina Madruga Carvalho1, Daniel Wilson Arruda Magalhaes1
1Biotechnology Center, Federal University of Paraíba, João Pessoa, Paraíba, Brazil.
Abstract:
Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, characterized by rapid proliferation, diffuse infiltration, and resistance to conventional therapies. Despite advances in surgery, radiotherapy, and chemotherapy, the prognosis remains dismal, with median survival rarely exceeding 15 months. The immunosuppressive and heterogeneous tumor microenvironment (TME), along with profound tumor-intrinsic resistance mechanisms, contributes significantly to treatment failure. Cardiotonic steroids (CTS), such as ouabain, have recently gained attention for their pleiotropic effects beyond Na+/K+-ATPase inhibition, including modulation of intracellular signaling, induction of cell death, and immune regulation. In GBM, ouabain has been shown to reduce tumor cell viability, impair migration, disrupt angiogenesis, and alter different signaling pathways. Although direct evidence of ouabain's effects on the GBM immune microenvironment is limited, findings from other models suggest that it can modulate both innate and adaptive immune responses, affecting T cells, regulatory T cells, dendritic cells, monocytes, and NK cells. While previous reviews have explored the anticancer and pharmacological aspects of cardiotonic steroids, the immunological dimension of ouabain's activity remains underrepresented. This review integrates current evidence on ouabain's dual actions in tumor biology and immune regulation, emphasizing its emerging therapeutic potential and the need for deeper investigation within high-grade glioma models.
Insights
Ouabain, a cardiotonic steroid, shows potential in treating glioblastoma (GBM) by impacting tumor cells and the immune microenvironment. Further research is needed to explore its therapeutic benefits in high-grade glioma.
Area of Science:
- Neuro-oncology
- Immunology
- Pharmacology
Background:
- Glioblastoma (GBM) is an aggressive brain tumor with poor prognosis due to treatment resistance and an immunosuppressive tumor microenvironment (TME).
- Conventional therapies offer limited survival benefits, highlighting the need for novel therapeutic strategies.
- Cardiotonic steroids (CTS), like ouabain, exhibit diverse biological activities beyond Na+/K+-ATPase inhibition.
Purpose of the Study:
- To review the dual actions of ouabain in glioblastoma, focusing on its effects on tumor biology and immune regulation.
- To highlight the emerging therapeutic potential of ouabain in high-grade gliomas.
- To emphasize the need for further investigation into ouabain's immunomodulatory effects in the GBM TME.
Main Methods:
- Literature review integrating evidence on ouabain's effects on GBM cell viability, migration, angiogenesis, and signaling pathways.
- Exploration of ouabain's potential immunomodulatory effects based on findings from other models.
- Synthesis of current research on CTS, with a specific focus on ouabain's role in glioblastoma.
Main Results:
- Ouabain has demonstrated efficacy in reducing glioblastoma cell viability, impairing migration, and disrupting angiogenesis.
- Ouabain may modulate both innate and adaptive immune responses, influencing various immune cell types.
- Evidence suggests ouabain impacts intracellular signaling and can induce cell death.
Conclusions:
- Ouabain presents a promising therapeutic avenue for glioblastoma, acting on both tumor cells and the immune microenvironment.
- Understanding ouabain's immunomodulatory functions is crucial for optimizing its therapeutic application in high-grade gliomas.
- Further dedicated research is warranted to fully elucidate ouabain's potential in glioblastoma treatment.
