Melatonin's Potential in Colorectal Cancer: Effects on Lipid Metabolism and Gut Microbiota

This summary is based on the scientific article Therapeutic Potential of Melatonin in Colorectal Cancer: Focus on Lipid Metabolism and Gut Microbiota by Shijia Pan et al., which explores the multifaceted role of melatonin in the prevention and treatment of colorectal cancer (CRC). Colorectal cancer is one of the most common gastrointestinal malignancies and a leading cause of cancer-related deaths worldwide. The development of CRC is influenced by various factors, and melatonin, a hormone primarily produced by the pineal gland, has been recognized for its regulatory effects on lipid metabolism and gut microbiota. The article reviews existing studies to highlight melatonin's potential to inhibit cancer cell growth, promote apoptosis (programmed cell death), reduce oxidative stress, and modulate immune responses, thereby suggesting melatonin as a promising candidate for CRC therapy.

The review summarizes existing studies on the role of melatonin in CRC, focusing on its effects on lipid metabolism and the gut microbiota. The researchers examined the interactions between melatonin, adipogenesis, lipogenesis, lipolysis, and gut microbiota composition and function. They also discussed melatonin's potential as an anti-cancer agent through various signaling pathways and physiological mechanisms.

Advanced experimental methods such as immunohistological techniques, radioimmunoassay, gas chromatography-mass spectrometry (GC–MS), high-performance liquid chromatography (HPLC), and ELISA were employed to analyze melatonin levels and their effects.

1. Maintaining Gastrointestinal Homeostasis:
   • Melatonin plays a critical role in maintaining gastrointestinal health and regulating circadian rhythms, subsequently influencing the gut microbiota composition.
   • It modulates the gut microbiota composition by promoting beneficial bacteria and reducing pathogenic bacteria.
2. Increase in Beneficial Bacteria:
   • Melatonin increases the abundance of beneficial bacteria like Akkermansia, which is associated with improved metabolic health.
   • It reduces harmful bacteria such as Alistipes and Anaerotruncus, linked to obesity and metabolic disorders.
3. Reduction in Obesity and Improved Metabolic Health:
   • Changes in the gut microbiota mediated by melatonin can lead to a reduction in obesity and improvements in overall metabolic health.
   • Melatonin's regulation of the gut microbiota helps in modulating lipid metabolism and reducing inflammation, thereby contributing to its anti-obesity effects.

1. Anti-Tumor Effects:
   • Melatonin exhibits anti-tumor properties by promoting apoptosis (programmed cell death) and inhibiting cell proliferation, migration, and invasion of cancer cells.
   • It activates apoptotic pathways and enhances the expression of pro-apoptotic proteins like cleaved caspase-3 and PARP.
2. Reduction of Oxidative Stress:
   • Melatonin acts as a potent antioxidant, reducing oxidative stress by scavenging free radicals and enhancing the activity of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx).
   • It modulates the expression of genes involved in oxidative stress response, such as Nrf2, and reduces the production of reactive oxygen species (ROS).
3. Enhancement of Immune Responses:
   • Melatonin enhances immune responses by regulating the activity of immune cells like macrophages and T cells.
   • It stimulates the production of cytokines such as IL-2 and IL-12, boosting the body's anti-tumor immune response.

Melatonin shows significant promise as a therapeutic agent for colorectal cancer by regulating lipid metabolism and maintaining gut microbiota balance. Its multi-faceted role in reducing obesity, enhancing immune responses, and directly inhibiting cancer cell growth positions it as a valuable candidate for further research and clinical application in CRC prevention and treatment.

Future studies should focus on optimizing dosing protocols and understanding the long-term effects of melatonin supplementation in cancer patients. Integrating melatonin into cancer care could offer a novel, holistic approach to managing colorectal cancer, ultimately improving patient outcomes and quality of life.