Melatonin boosts the immune system to fight cancer cells.

Melatonin's Anti-Cancer Potential: Inhibition of Initiation, Progression, and Metastasis

Written by: Mécène Market



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.


This summary is based on the scientific review article by Russel J. Reiter et al. entitled Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis, which explores the potential of melatonin (MLT) as a treatment for various cancers. Cancer is a major cause of death worldwide, 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, primarily known for regulating sleep-wake cycles, has emerged as a significant anti-cancer agent, impacting cancer initiation, progression, and metastasis through multiple biochemical and molecular pathways.

Mechanisms of Melatonin's Anti-Cancer Potential

Melatonin, beyond its well-known role in regulating sleep-wake cycles, exhibits significant anti-cancer properties.

Its multi-faceted actions impact various stages of cancer development, from inhibiting initial cell growth to preventing metastasis.

These mechanisms involve melatonin's ability to interfere with cancer cell proliferation, induce apoptosis, inhibit angiogenesis, modulate the immune system, and exert both antioxidative and pro-oxidative effects.

This section looks into the specific biochemical and molecular pathways through which melatonin exerts its anti-cancer effects, highlighting its potential as a powerful adjunct in cancer therapy.



Melatonin acts as a strong antioxidant. It helps clear out harmful molecules called free radicals that can damage DNA and start cancer. By doing this, melatonin protects the DNA in cells and lowers the chance of cancer starting.

It also helps boost the activity of other antioxidants in the body, making cells even better at defending against DNA damage.

Illustration of the biochemical and molecular pathways through which melatonin exerts its anti-cancer effects.

Telomerase Activity Reduction

Melatonin stops an enzyme called telomerase in cancer cells. Telomerase helps cancer cells keep dividing endlessly.

By stopping this enzyme, melatonin helps shorten the cancer cells' lifespan, making it harder for tumors to grow.

Shorter telomeres make cancer cells unstable and less likely to keep growing. This helps prevent tumors from starting and growing.

Inhibition of Cancer Progression

Cell Proliferation and Apoptosis

Melatonin slows down the growth of cancer cells and helps trigger their death, a process called apoptosis. It affects important pathways in the cells, including those related to estrogen and how cells get their energy. 

By cutting off energy sources and disrupting signals that tell cancer cells to grow, melatonin helps stop cancer from spreading.


Melatonin reduces the levels of a molecule called endothelin-1 (ET-1) that helps tumors grow new blood vessels. 

Tumors need these blood vessels to get nutrients and oxygen. By stopping ET-1, melatonin cuts off the tumor's blood supply, slowing its growth and making it harder for the tumor to survive.

Inhibition of Metastasis

Prevention of Metastatic Spread

Melatonin interferes with the processes involved in metastasis, such as the invasion of cancer cells into the vascular system and creation of secondary tumors at distant sites.

It stops cancer cells from sticking together, moving, and invading other tissues. It also promotes apoptosis, which is the process of programmed cell death, helping to eliminate cancer cells that might spread. This is very important for preventing cancer from spreading.

Melatonin boosts the immune system to fight cancer cells.

Immune System Modulation

Melatonin boosts the body's immune system to fight cancer. It increases the production of immune cells and chemicals that help recognize and destroy cancer cells. 

By boosting the activity of natural killer cells and other immune system parts, melatonin makes the body's defenses stronger. This makes it harder for cancer cells to spread and form new tumors. 

Melatonin also reduces the immune-suppressing effects that cancer cells have on the body, making the immune system more effective.

Role of Melatonin in Colorectal Cancer Management

Dietary Influence and Apoptosis Promotion

Colorectal cancer (CRC) is a major health concern as it is one of the most common cancers and the second leading cause of cancer deaths worldwide. 

CRC is often linked to a diet high in meat and low in fiber-rich vegetables and fruits. Research by Wei and colleagues found that melatonin helps kill colon cancer cells by affecting a process involving a protein called HDAC4. 

By stopping HDAC4 from entering the cell nucleus, melatonin promotes cancer cell death. This is important because fiber-rich foods, which are good for you, have more melatonin than meat.

Inhibition of Endothelin-1 (ET-1)

Another study by Leon et al. explored melatonin's role in controlling the growth of colorectal cancer cells using human-derived Caco-2 and TP4 colon cancer cell lines.

They found that melatonin reduces the production of ET-1, a peptide secreted by many solid tumors that promotes cancer cell survival, proliferation, blood vessel ingrowth, and apoptosis repression.

A doctor discussing melatonin therapy with a cancer patient.

Therapeutic Implications of Melatonin in Cancer Treatment

The diverse anti-cancer mechanisms of melatonin suggest its potential as a valuable adjunct therapy in cancer treatment. 

Here, we explore the specific therapeutic implications of melatonin in enhancing conventional cancer therapies, reducing toxicity, and restoring drug sensitivity.

Enhancement of Conventional Cancer Therapies

Melatonin has been shown to improve the effectiveness of conventional cancer treatments such as chemotherapy and radiotherapy.

By making cancer cells more sensitive to these treatments, melatonin helps kill cancer cells more effectively. This means doctors might be able to use lower doses of chemotherapy, reducing side effects.

Reduction of Toxic Side Effects

One of the advantages of melatonin is its ability to protect normal cells from the damaging effects of conventional cancer treatments.

Melatonin's antioxidative properties reduce the oxidative stress and damage that healthy cells endure during chemotherapy and radiotherapy.

This protective effect helps in reducing the incidence and severity of side effects, thereby improving patients' overall quality of life during treatment.

Restoration of Drug Sensitivity

Melatonin has been found to reverse the resistance that some cancers develop against conventional therapies. This is particularly significant for patients who have advanced-stage cancers where resistance to treatment is a major hurdle. 

Melatonin enhances the efficacy of chemotherapy and radiotherapy by restoring cancer cells' sensitivity, potentially leading to better clinical outcomes.

Laboratory research on the effects of melatonin in cancer treatment.

Clinical Validation and Future Research

Given the promising preclinical and early clinical findings, extensive clinical trials are warranted to further explore and validate the use of melatonin in cancer therapy.

These studies should find the best doses, check long-term safety, and see how well melatonin works with other treatments. Understanding how melatonin targets cancer cells can help develop better, more personalized treatments.

The Potential of Melatonin in Cancer Therapy

Melatonin demonstrates significant potential in cancer therapy due to its various anti-cancer properties. It effectively interferes with various stages of cancer development, from initiation to metastasis, through its actions as an antioxidant, modulator of cell proliferation and apoptosis, inhibitor of angiogenesis, and immune system enhancer.

These actions highlight melatonin's ability to combat cancer on multiple fronts, making it a promising candidate for inclusion in comprehensive cancer treatment strategies.

Existing research provides a strong foundation for the therapeutic use of melatonin in oncology. However, further research and extensive clinical trials are essential to fully understand and harness its potential.

By continuing to research and confirm melatonin’s effects on different cancers, doctors might use this natural hormone as a regular part of cancer care, offering patients a treatment that works well and has fewer side effects.


Reiter, R. J., Rosales-Corral, S. A., Tan, D. X., Acuna-Castroviejo, D., Qin, L., Yang, S. F., & Xu, K. (2017). Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis. International journal of molecular sciences18(4), 843.