ArticleJournal of molecular medicine (Berlin, Germany)2021
MT1 and MT2 melatonin receptors play opposite roles in brain cancer progression.
Article in Journal of molecular medicine (Berlin, Germany), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Melatonin in glioblastoma therapy: clinical promise and mechanistic insights from bench to bedside.Neurosurgical review · 2026Pooled it
- Melatonin receptor signaling in human pathologies: from molecular mechanisms to therapeutic targets.Function (Oxford, England) · 2026Review
- Review
- Single-cell RNA sequencing provides new insights into the interaction between astrocytes and neurons after spinal cord injury in mice.Biochemistry and biophysics reports · 2025Article
- CuO nanoparticles for glioma treatment in vitro and in vivo.Scientific reports · 2024Article
- Brain washing and neural health: role of age, sleep, and the cerebrospinal fluid melatonin rhythm.Cellular and molecular life sciences : CMLS · 2023Review
- Melatonin Treatment in Kidney Diseases.Cells · 2023Review
- MEL-Index: Estimation of Tissue Melatonin Levels Using Gene Expression Data.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Review
- Neuronal-driven glioma growth requires Gαi1 and Gαi3.Theranostics · 2021Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Primary brain tumors remain among the deadliest of all cancers. Glioma grade IV (glioblastoma), the most common and malignant type of brain cancer, is associated with a 5-year survival rate of < 5%. Melatonin has been widely reported as an anticancer molecule, and we have recently demonstrated that the ability of gliomas to synthesize and accumulate this indolamine in the surrounding microenvironment negatively correlates with tumor malignancy. However, our understanding of the specific effects mediated through the activation of melatonin membrane receptors remains limited. Thus, here we investigated the specific roles of MT1 and MT2 in gliomas and medulloblastomas. Using the MT2 antagonist DH97, we showed that MT1 activation has a negative impact on the proliferation of human glioma and medulloblastoma cell lines, while MT2 activation has an opposite effect. Accordingly, gliomas have a decreased mRNA expression of MT1 (also known as MTNR1A) and an increased mRNA expression of MT2 (also known as MTNR1B) compared to the normal brain cortex. The MT1/MT2 expression ratio negatively correlates with the expression of cell cycle-related genes and is a positive prognostic factor in gliomas. Notably, we showed that functional selective drugs that simultaneously activate MT1 and inhibit MT2 exert robust anti-tumor effects in vitro and in vivo, downregulating the expression of cell cycle and energy metabolism genes in glioma stem-like cells. Overall, we provided the first evidence regarding the differential roles of MT1 and MT2 in brain tumor progression, highlighting their relevance as druggable targets. KEY MESSAGES: • MT1 impairs while MT2 promotes the proliferation of glioma and medulloblastoma cell lines. • Gliomas have a decreased expression of MT1 and an increased expression of MT2 compared to normal brain cortex. • Tumors with a high MT1/MT2 expression ratio have significantly better survival rates. • Functional selective drugs that simultaneously activate MT1 and inhibit MT2 downregulate the expression of cell cycle and energy metabolism genes in glioma stem-like cells and exert robust anti-tumor effects in vivo.
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