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Updated: Feb 4, 2026
Invasive Behavior of Human Breast Cancer Cells in Embryonic Zebrafish
Published on: April 25, 2017
Melatonin inhibits breast cancer cell invasion through modulating DJ-1/KLF17/ID-1 signaling pathway
Gamal H El-Sokkary1, Ismail Ahmed Ismail2,3, Saber H Saber2
1Department of Zoology, Faculty of Science, Assiut University, Assiut, Egypt.
Abstract:
Breast cancer is the most common neoplastic disorder diagnosed in women. The main goal of this study was to explore the effect of melatonin against breast cancer metastasis and compared this with the actions of taxol (a well-known chemotherapeutic drug), and the impact of their combination against breast cancer metastasis. Melatonin showed no cytotoxic effect while taxol showed antiproliferative and cytotoxic effects on MCF-7 and MDA-MB-231 cells. Furthermore, melatonin inhibited the generation of reactive oxygen species. Melatonin and taxol clearly decreased cell migration and invasion at low doses, especially those matching the normal physiological concentration at night. Melatonin and taxol markedly reduced DJ-1 and ID-1 and increased KLF17 messenger RNA and protein expression levels. The present results also showed that melatonin and taxol induced GSK3-β nuclear and Snail cytosolic localization. These changes were accompanied by a concurrent rise in E-cadherin expression. The above data show that normal levels of melatonin may help in preventing breast cancer metastasis through inhibiting DJ-1/KLF17/ID-1 signaling pathway. The combination of melatonin and taxol is a potent candidate against breast cancer metastasis, better than using melatonin or taxol as a single drug.
Insights
Melatonin, at normal physiological levels, may prevent breast cancer metastasis by inhibiting the DJ-1/KLF17/ID-1 pathway. Combining melatonin with taxol shows greater efficacy against metastasis than either agent alone.
Area of Science:
- Oncology
- Molecular Biology
- Endocrinology
Background:
- Breast cancer is a prevalent neoplastic disorder in women.
- Metastasis is a critical factor in breast cancer progression and mortality.
- Melatonin, a hormone, and taxol, a chemotherapeutic, are investigated for their anti-metastatic potential.
Purpose of the Study:
- To investigate the anti-metastatic effects of melatonin in breast cancer.
- To compare melatonin's efficacy with taxol.
- To evaluate the combined effect of melatonin and taxol on breast cancer metastasis.
Main Methods:
- Cell lines (MCF-7 and MDA-MB-231) were treated with melatonin and taxol.
- Assessed cytotoxicity, proliferation, reactive oxygen species generation, cell migration, and invasion.
- Analyzed gene and protein expression of DJ-1, ID-1, KLF17, GSK3-β, Snail, and E-cadherin.
Main Results:
- Taxol exhibited antiproliferative and cytotoxic effects; melatonin did not show cytotoxicity but inhibited reactive oxygen species.
- Both melatonin and taxol reduced cell migration and invasion, particularly at physiological concentrations.
- Melatonin and taxol modulated key signaling molecules (DJ-1, ID-1, KLF17, GSK3-β, Snail) and increased E-cadherin expression.
Conclusions:
- Physiological levels of melatonin may inhibit breast cancer metastasis via the DJ-1/KLF17/ID-1 pathway.
- The combination of melatonin and taxol is a promising therapeutic strategy against breast cancer metastasis, superior to monotherapy.
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