Melatonin's Role in Colorectal Cancer

Melatonin: A Promising Adjunct in Colorectal Cancer Treatment

Written by: Mécène Market

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Time to read 5 min

Medical Disclaimer: This article is for informational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay seeking it because of something you have read on this website. The information in this article is based on a scientific review and should not be used as the sole basis for treatment decisions. Always consult with a healthcare professional before starting any new treatment or therapy.

Background

This summary is based on the scientific review article by Kvietkauskas et al. entitled The Role of Melatonin in Colorectal Cancer Treatment: A Comprehensive Review, which explores the potential of melatonin (MLT) as a treatment for colorectal cancer (CRC). CRC is a major cause of cancer-related deaths globally, with current treatments involving surgery, chemotherapy, and radiotherapy. However, these treatments often have limited effectiveness, especially in advanced stages due to resistance and side effects.

Melatonin: The Endogenous Hormone

Melatonin (MLT), also known as N-acetyl-5-methoxytryptamine, is a hormone that plays a crucial role in regulating sleep and circadian rhythms. It was discovered in 1958 by Aaron Lerner, a North American dermatologist at Yale University. 


For many years, melatonin was thought to be synthesized exclusively in the pineal gland, a small gland in the brain, from the amino acid tryptophan in response to darkness.


Receptor Interaction


In humans and mammals, melatonin exerts its effects through specific receptors known as MT1 and MT2, which are encoded by the MTNR1A and MTNR1B genes, respectively. These receptors are expressed in various parts of the central nervous system and peripheral organs.


Another binding site, MT3, has been identified as a melatonin-sensitive form of quinone reductase 2, involved in detoxification processes within cells. However, MT3 does not fully qualify as a melatonin receptor.


Melatonin also interacts with cytoplasmic proteins like calmodulin and tubulin and nuclear receptors like RORα/RZR, contributing to its diverse physiological effects.

Melatonin's Potential in CRC Treatment: Mechanisms of Action

Melatonin has shown promising anti-cancer properties in various studies, making it a potential adjunct in colorectal cancer (CRC) treatment. Its ability to inhibit cancer cell growth, induce apoptosis, and reduce metastasis makes it a valuable candidate for enhancing current cancer therapies.

Inhibition of Cancer Cell Growth

Melatonin can block cancer cells from multiplying by interfering with their energy sources and growth signals. Specifically, it reduces the uptake of linoleic acid, an essential energy source for tumors. It also inhibits key signaling pathways that cancer cells use to proliferate, such as the cAMP/PKA signaling pathway, thereby slowing down their growth.

Promotion of Apoptosis

Melatonin helps trigger programmed cell death in cancer cells through several biochemical pathways. This process, known as apoptosis, is crucial for eliminating cancer cells from the body. 


Melatonin can activate various proteins and enzymes that lead to cell death, including those in the Bcl-2 family and the NF-κB signaling pathway. For instance, melatonin can enhance the activation of caspases, which are enzymes that play essential roles in programmed cell death.

Inhibition of Angiogenesis

Angiogenesis, the formation of new blood vessels, is essential for tumor growth as it supplies the tumor with nutrients and oxygen. 


Melatonin can prevent this process by inhibiting factors like vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1-alpha (HIF-1α). This reduces the tumor's ability to grow and spread. 


Studies have shown that melatonin can downregulate the expression of HIF-1α and VEGF, which are critical for new blood vessel formation in tumors.

Immune System Modulation

Melatonin enhances the body's immune response against cancer cells. It stimulates the production of various immune cells and cytokines, such as interleukin-2 (IL-2), which help identify and destroy cancer cells. This immune-boosting effect makes melatonin a valuable addition to cancer therapy. 


Additionally, melatonin can modulate the activity of macrophages and natural killer cells, further enhancing the immune system's ability to target cancer cells.

Antioxidative and Pro-oxidative Effects

Melatonin has dual roles as both an antioxidant and a pro-oxidant. As an antioxidant, it protects normal cells from damage caused by oxidative stress by scavenging free radicals and upregulating antioxidant enzymes like superoxide dismutase (SOD) and glutathione peroxidase (GPx).


However, In cancer cells, melatonin can increase oxidative stress, destroying them. This selective effect helps target cancer cells while preserving healthy ones. High concentrations of melatonin can induce the production of reactive oxygen species (ROS) in cancer cells, promoting apoptosis.

A man getting an assessment for cancer

Research Findings: Melatonin's Role in Colorectal Cancer

In Vitro Studies

Laboratory studies have shown that melatonin can effectively inhibit CRC cell growth and induce apoptosis. It also enhances the effectiveness of chemotherapy drugs.


Studies on CRC cell lines have demonstrated that melatonin can increase the sensitivity of cancer cells to drugs like doxorubicin and 5-fluorouracil (5-FU), making them more effective at lower doses.


For example, melatonin has been shown to modulate the expression of microRNAs involved in drug resistance, thereby enhancing the cytotoxic effects of chemotherapy agents.

In Vivo Studies

Animal studies support these findings, showing reduced tumor growth and increased survival rates when melatonin is used alongside traditional cancer treatments.


In rodent models, melatonin treatment has resulted in smaller tumor sizes and lower metastasis rates, indicating its potential to improve outcomes in CRC.


These studies have demonstrated that melatonin can inhibit tumor growth by modulating various signaling pathways, including the MAPK/ERK and PI3K/AKT pathways, which are crucial for cell proliferation and survival.

Clinical Trials

Some early clinical trials suggest that melatonin can improve the quality of life and enhance the effects of chemotherapy in cancer patients.


Patients receiving melatonin alongside their chemotherapy regimens have reported better overall well-being, fewer side effects, and improved response rates.


However, more research is needed to determine the optimal dosage and administration method. For instance, a study involving advanced CRC patients found that melatonin, when administered at a dose of 20 mg/day, improved the patients' response to chemotherapy and reduced the incidence of chemotherapy-induced side effects such as thrombocytopenia and neurotoxicity.

A person in the lab conducting an experiment on melatonin for cancer

Future Directions and the Potential of Melatonin in Colorectal Cancer Treatment

Future research should focus on determining the optimal dosing regimens and understanding the long-term effects of melatonin use in cancer therapy.


Additionally, further studies are needed to explore the synergistic effects of melatonin with other anti-cancer agents and its potential role in preventing cancer recurrence.

Meet the Author

Dr. James Pendleton

Dr. James Pendleton is a primary care physician specializing in a naturopathic approach to family medicine. He has nurtured a family practice in Seattle, directed a VIP medical center in Abu Dhabi, published several books and scientific articles, and designed innovative nutritional supplements for manufacturers worldwide.

REFERENCES

Kvietkauskas, M., Zitkute, V., Leber, B., Strupas, K., Stiegler, P., & Schemmer, P. (2020). The role of melatonin in colorectal cancer treatment: a comprehensive review. Therapeutic advances in medical oncology12, 1758835920931714. https://doi.org/10.1177/1758835920931714