# Melatonin's oncostatic effects in experimental breast cancer: A systematic review of dose-response and apoptotic mechanisms in animal models

## TL;DR

This paper reviews how melatonin may reduce breast cancer in animal models by promoting cell death, but more research is needed to understand the exact mechanisms.

## Contribution

The study systematically reviews melatonin's oncostatic effects in breast cancer animal models, highlighting dose-response and apoptotic mechanisms.

## Key findings

- Melatonin inhibited tumorigenesis in three studies with the lowest risk of bias.
- Six studies showed a reduction in tumors correlated with apoptosis.
- High melatonin doses induced tumor reduction via apoptosis in animal models.

## Abstract

•The high mortality rate associated with breast cancer makes it an important neoplasm.•Melatonin may modulate breast cancer progression, influencing proliferation and apoptosis.•Melatonin inhibited tumorigenesis in three studies with the lowest risk of bias.

The high mortality rate associated with breast cancer makes it an important neoplasm.

Melatonin may modulate breast cancer progression, influencing proliferation and apoptosis.

Melatonin inhibited tumorigenesis in three studies with the lowest risk of bias.

Breast cancer remains a major health concern for women because of its prevalence and high morbidity and mortality rates. Metastasis represents the most severe prognosis, and many studies have been conducted to understand the mechanisms involved in cell migration and the factors influencing this process.

To evaluate the effects of melatonin on breast cancer cells through a systematic literature review.

Systematic review of the literature was carried out through PubMed, Embase and Web of Science as scientific search platforms using Population, Intervention, Comparison, and Outcome (PICO) with the keywords (P) “rat” or “murine”; (I) “melatonin’’, “pineal’’ and “indolamine’’; (C) “breast cancer model’’, “mammary cancer model’’ and “breast tissue’’ and (O) “proliferation” and “cell migration.” The inclusion criteria were full-text, open-access articles in Portuguese, English, or Spanish that focused on the antioxidant and proapoptotic actions of melatonin on breast cancer cells. The exclusion criteria were articles published >20-years ago, those with missing methodological information, and those not describing the dosage and specificity of the research product used. The findings of each included study were structured in tables with details about the sample size, dose of melatonin, and route of administration. The quality of evidence was assessed using the Cochrane risk-of-bias tool. This study was registered in PROSPERO (n° CRD42025635531).

A total of 257 articles were selected from the databases; 25 were read in full, resulting in 10 articles selected for this systematic review, with a total population of 756 animals studied. From the studies analyzed, six showed a reduction in tumors in correlation with the apoptosis process. This review shows that melatonin can inhibit tumorigenesis in three studies with the lowest risk of bias, which reinforces the oncostatic action of melatonin. However, several studies have combined other substances to evaluate their oncostatic action, making it difficult to infer the mechanisms involved. Further studies are necessary to elucidate the mechanisms through which melatonin acts in mammary carcinogenesis.

The literature shows that in animal models of breast tumors, high doses of melatonin can induce tumor reduction by cell death through apoptosis. However, further studies are required to understand the mechanisms by which this hormone acts in mammary carcinogenesis.