Melatonin inhibits breast cancer cell invasion through modulating DJ‐1/KLF17/ID‐1 signaling pathway

• Published in: Journal of cellular biochemistry Vol. 120; no. 3; pp. 3945 - 3957
• Main Authors: El‐Sokkary, Gamal H., Ismail, Ismail Ahmed, Saber, Saber H.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.03.2019
• Subjects: Breast cancer; breast cancer invasion; Cancer; Cell adhesion & migration; Cell migration; Cytotoxicity; DJ‐1; E-cadherin; Gene expression; KLF17; Localization; Melatonin; Metastases; Metastasis; Paclitaxel; Proteins; Reactive oxygen species; Ribonucleic acid; RNA; Signal transduction; Signaling; Taxol; taxol; DJ-1; melatonin; breast cancer invasion; KLF17
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.27678

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. Melatonin works through the recently discovered DJ‐1/KLF17/ID‐1 signaling pathway to inhibit breast cancer invasion. The combination therapy of melatonin and taxol is suggested as a promising candidate therapy against breast cancer cell invasion and metastasis. Melatonin induced nuclear localization of GSK3β with a concurrent cytosolic localization of Snail.