Melatonin in cancer biology: pathways, derivatives, and the promise of targeted delivery

Abstract

Melatonin, historically recognized for its primary role in regulating circadian rhythms, has expanded its influence particularly due to its wide range of biological activities. It has firmly established itself in cancer research. To highlight its versatility, we delved into how melatonin interacts with key signaling pathways, such as the Wnt/β-Catenin, PI3K, and NF-κB pathways, which play foundational roles in tumor development and progression. Notably, melatonin can intricately modulate these pathways, potentially affecting various cellular functions such as apoptosis, metastasis, and immunity. Additionally, a comprehensive review of current clinical studies provides a dual perspective. These studies confirm melatonin’s potential in cancer management but also underscore its inherent limitations, particularly its limited bioavailability, which often relegates it to a supplementary role in treatments. Despite this limitation, there is an ongoing quest for innovative solutions and current advancements include the development of melatonin derivatives and cutting-edge delivery systems. By synthesizing the past, present, and future, this review provides a detailed overview of melatonin’s evolving role in oncology, positioning it as a potential cornerstone in future cancer therapeutics.

Keywords:

• Melatonin
• cancer
• signaling pathways
• derivatives
• delivery
• nanoparticles

Authors’ contributions

Conceptualization, Y.Y., H.T., P.P., H.Z., S.D., W.G., Q.D., Z.Z., J.L., and Z.S.; resources, S.D., W.G., Q.D., and Z.Z.; data curation, Y.Y., H.T., and P.P.; writing–original draft preparation, Y.Y., and H.T.; writing–review and editing, Y.Y., H.T., J.L., and Z.S.; visualization, Y.Y., H.T., P.P., and H.Z.; supervision, J.L. and Z.S.; project administration, J.L. and Z.S.; funding acquisition, J.L. and Z.S. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

The authors declare no conflicts of interest.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China (81702485), The Educational fund item of Liaoning Province (LJKZ0845), Research on cancer prevention and treatment in 2022 by Chen Xiaoping Science and Technology Development Foundation of Hubei Province (CXPJJH122002-075), and the Foundation for Young Scientists Cultivation of Dalian Medical University (508028).