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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.