# Glioblastoma and Melatonin’s Effects: A Narrative Review

## TL;DR

This review explores how melatonin, a natural molecule, might help treat glioblastoma, a deadly brain tumor, by influencing cancer cell mechanisms, though more research is needed.

## Contribution

The paper reviews recent findings on melatonin's potential as a complementary treatment for glioblastoma by modulating intracellular pathways.

## Key findings

- Melatonin shows antioxidant and anticancer properties in glioblastoma cells.
- Melatonin may act as a 'smart killer' by targeting cancer cells specifically.
- Clinical trials are lacking, and more studies are needed to confirm melatonin's efficacy in glioblastoma patients.

## Abstract

Glioblastoma is one of the most aggressive and difficult-to-treat brain tumors, with patient survival remaining very limited despite advances in chemotherapy, surgery, and radiotherapy. For this reason, new strategies are needed to improve treatment effectiveness and reduce side effects. Melatonin is a natural molecule produced by the pineal gland, best known for regulating sleep, but growing evidence suggests that it may also have antioxidant and anticancer properties. This review summarizes current knowledge on glioblastoma and examines recent studies showing how melatonin can influence the cellular mechanisms involved in tumor growth and progression. Overall, melatonin appears to be a promising complementary agent to conventional treatments and may offer new perspectives for future research in tumor management. To date, however, the data are fragmentary and unclear; several experimental studies do not demonstrate clinical efficacy, and only a few clinical studies are available.

Glioblastoma (GB) is an extremely aggressive, highly invasive brain tumor of astrocytic or oligodendrocyte glial origin. This tumor often infiltrates adjacent healthy brain tissue and can migrate significant distances from the primary tumor site. Given the poor overall survival of GB patients and the limited efficacy of current local and systemic treatments, new therapeutic strategies are needed to improve outcomes, reduce side effects, and enhance patients’ quality of life. In recent years, the potential chemotherapeutic effects of natural molecules have been investigated, either as primary agents or in combination with established chemotherapies in various types of cancer. Melatonin (MLT, N-acetyl-5-methoxytryptamine) is an endogenous indolamine primarily secreted by the pineal gland. MLT appears to discriminate between normal and tumoral cellular contexts and to modulate appropriate actions, thereby acting as a “smart killer” against cancer cells; however, further studies are needed to clarify this apparently paradoxical behavior. This review aims to summarize recent findings on the potential regulatory role of MLT in the modulation of key intracellular pathways in GB, underlining its potential role as a complementary adjuvant to conventional therapies. The clinical advantage of MLT in GB patients has not been demonstrated in randomized controlled trials; therefore, multicenter studies with well-defined objectives, appropriate dosage schedules, and clear patient classification are needed.