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

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.

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.

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.

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 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.

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.

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.

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.

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.

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.

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.

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.