Melatonin's Potential Role in Cancer Prevention

Cancer

Uncontrolled cell division and proliferation are hallmarks of the complex and widespread group of disorders known as cancer. Even with all the advancements in medicine, cancer is still a serious worldwide health problem.

I. Cancer Causes

·       Genetic Factors: A major contributing factor to the development of cancer is genetic mutations. A person may either inherit or acquire these mutations during their lifetime. To solve the riddles surrounding the onset of cancer, it is essential to comprehend how genetic predisposition and environmental variables interact.

·       Environmental variables: The chance of acquiring cancer is increased by exposure to specific environmental variables. Tobacco smoke, UV light, and certain chemicals are examples of carcinogens that can damage cellular DNA and cause malignant cells to develop. Diet and exercise habits are two other lifestyle factors that affect cancer risk.

·       Viral Infections: Viral infections have been connected to some malignancies. For example, hepatitis B and C raise the risk of liver cancer, whereas the human papillomavirus (HPV) is linked to cervical cancer. Determining specific preventative measures requires an understanding of these viral relationships.

II. Cancer Types

·       Carcinomas: The epithelial cells that cover the interior and exterior surfaces of the body are the source of carcinomas, which are the most prevalent kind of cancer. Common malignancies such as those of the breast, lung, prostate, and colorectal regions fall under this group.

·       Sarcomas: Sarcomas arise in the connective tissues of the body, including blood vessels, muscles, and bones. Although they are less common than carcinomas, they nonetheless need specific treatment methods.

·       Leukemias are tumors that impact the bone marrow and blood. An excess of immature blood cells results from abnormalities in blood cell synthesis, which impairs blood's ability to function normally.

·       Lymphomas: The lymphatic system is an important part of the immune system. Lymphomas attack this system. The two primary subtypes are non-Hodgkin's lymphoma and Hodgkin's lymphoma.

·       Cancers of the Central Nervous System: These tumors impact the brain and spinal cord. Examples of malignancies of the central nervous system are medulloblastomas, meningiomas, and gliomas; each requires a unique treatment strategy.

Progress in the Management of Cancer

·       Immunotherapy: Immunotherapy stimulates the immune system to identify and eliminate cancerous cells. In this quickly developing area, therapeutic vaccinations, CAR-T cell therapy, and checkpoint inhibitors are intriguing directions.

·       Targeted Therapies: These treatments target certain chemicals that contribute to the development of cancer. By tailoring treatment according to the genetic composition of a patient's cancer cells, precision medicine enables less harmful and more successful treatments.

·       Genomic Medicine: New insights into the genetics of cancer are made possible by developments in genomic research. Oncology is being revolutionized by personalized treatment strategies that are based on the distinct genetic makeup of each patient's disease.

·       Liquid Biopsies: In liquid biopsies, blood samples are examined for signs of genetic abnormalities and biomarkers associated with cancer. This non-invasive method helps with possible relapse identification, treatment response tracking, and early detection.

Melatonin

The body's natural hormone melatonin is essential for controlling the circadian rhythm, which is the cycle of wakefulness and sleep. It is secreted in a certain manner, rising in the evening as darkness falls and reaching its peak throughout the night to promote sound sleep. It is mostly produced by the pineal gland in the brain. The effect of this hormone spans a wide range of essential human health processes, even beyond the control of sleep. Melatonin has a wide range of other uses that support general health in addition to its part in the sleep cycle. Its antioxidant qualities lessen the harm that free radicals do to cells by preventing oxidative stress. This trait may potentially help prevent several age-related illnesses and ailments in addition to supporting cellular health.

Melatonin has been shown to play a role in immune system regulation in studies. It helps the body fight infections and perhaps lowers the risk of some diseases by regulating the immune response. Furthermore, the anti-inflammatory qualities of melatonin contribute to immune system homeostasis, which is essential for general health. Moreover, the effects of melatonin extend to mental health and mood management. Because of its potential to interact with brain neurotransmitters, research indicates that it may have a role in the management of mood disorders such as anxiety and depression. Its importance goes beyond sleep management, as evidenced by its capacity to improve mood and reduce symptoms of seasonal affective disorder (SAD) [1].

Melatonin is primarily produced by the pineal gland; however, it is also present in tiny levels in some meals. Foods with trace amounts of melatonin include cereals, tomatoes, olives, cherries, and grapes. Because beer has a comparatively greater melatonin concentration than other drinks, it has drawn attention. However, there are general health concerns associated with alcohol intake, so caution is advised. Supplemental melatonin has gained popularity as a treatment for several sleep problems, including jet lag and insomnia. These pills, which are available over the counter, provide an option for those who experience sleep difficulties. They should be used cautiously, though, as suggested dosages usually start at 1 mg or less, and greater amounts can have negative effects including grogginess.

Even with all its advantages, using melatonin supplements needs caution. High dosages and prolonged usage may have adverse effects that include fracture risk and interference with the hormone's normal production. Furthermore, the efficiency of melatonin supplementation varies from person to person and is limited by its solubility in water, which influences absorption. Most melatonin supplements are made in labs and are used to treat sleep problems such as insomnia, delayed sleep-wake phase disorder, and jet lag. Different doses are recommended; the lowest doses should be no more than 1 mg. It is best to stay away from higher dosages (5 or 10 mg) due to potential adverse effects including grogginess.

Melatonin binds receptors (MT1 and MT2) in the hypothalamus suprachiasmatic nucleus (SCN) to regulate the circadian rhythm. This binding initiates downstream signaling cascades by phospholipase C activation, neurotransmitter release modification, and inhibiting cAMP signal transduction. Immunological response, mood control, sleep regulation, antioxidant activity, and fertility are among its physiological functions [2].

Role of Melatonin in Cancer

With its wide range of anticancer properties, melatonin is an important component of cancer treatment. These include triggering programmed cell death, preventing the growth, and spread of tumors, and lessening the adverse effects of standard cancer treatments like radiation and chemotherapy.

Melatonin is an effective adjuvant medication to traditional cancer therapy, as demonstrated by clinical research. The hormone has demonstrated potential in the management and prevention of several malignancies, including colorectal, gastric, prostate, and breast cancers. Melatonin's promise as a therapeutic agent has been further supported by the demonstration of substantial anticancer effects at the pharmacological concentration of 1 mM.

Diving into Mechanisms

The effects of melatonin on cancer are not limited to one mechanism. The hormone inhibits mechanisms that lead to apoptosis, angiogenesis, proliferation, and metastasis. Through its effects on carcinogenesis and indirect disruption of the circadian cycle, it mitigates the pathogenesis of cancer by interfering with the beginning, development, and advancement of tumors [3].

·       Improving Traditional Treatments

Melatonin in conjunction with traditional medications has demonstrated potential for increasing cancer sensitivity for both solid and liquid tumors. Melatonin has the potential to be used in conjunction with other cancer treatments, even in the face of some contradictory findings that emphasize the need for more in vivo research and clinical trials.

·       Changing the Immune Response

Melatonin's potential for treating cancer is further enhanced by its effect on the immune system. Melatonin has been shown to strengthen the immune system's defense against cancer cells. Melatonin helps identify and eradicate malignant cells by enhancing the activity of immune cells including T lymphocytes and natural killer cells.

·       Relationship between Growth Factors and Hormones

Interactions between the hormone melatonin and other hormones and growth factors linked to the advancement of cancer have been noted. Melatonin, for example, has the potential to suppress the release of estrogen, a hormone that has been connected to the emergence of some forms of breast cancer. Furthermore, the insulin-like growth factor (IGF) pathway, which is linked to cell division and growth, may be disrupted by melatonin [4].

Preclinical and Clinical Trials of Melatonin in Cancer

Strong antioxidant melatonin protects DNA from oxidative damage in several ways. It actively scavenges free radicals, suppresses pro-oxidative enzymes, increases DNA repair, reduces metal-induced DNA damage, and promotes antioxidant enzymes. Melatonin has been shown in a recent study to lessen DNA damage and improve the anticancer impact of cisplatin in tumor-bearing mice. Furthermore, it demonstrated a noteworthy decrease in the generation of micronuclei brought about by γ-radiation in HeLa and MRC5 cells, demonstrating its scavenging action and augmentation of DNA repair pathways. In oral squamous cell carcinoma, melatonin also reduces the cytotoxic effect of arecoline by safeguarding DNA integrity and activating antioxidant enzymes [3].

One week before radiation exposure, pretreating breast cancer cells with melatonin inhibited proliferation, cell cycle arrest, and the expression of DNA-PKcs mRNA and RAD51. Furthermore, melatonin showed antiproliferative, anti-migratory, and proapoptotic actions in colon cancer cells by downregulating the NF-κB/iNOS and PI3K/AKT signaling pathways when coupled with 5-fluorouracil. Melatonin significantly downregulated the expression of the HIF-1α gene and protein, inhibiting the proliferation of cancer stem cells obtained from ovarian cancer cells and suppressing the development of breast cancer cells both in vitro and in vivo [4].

Melatonin has a remarkable effect on the immune system because it increases immune cell survival, optimizes cell metabolism in the tumor microenvironment, and regulates the release of cytokines. It decreases regulatory T cells and the expression of Forkhead box p3 in gastric cancer cells while increasing the generation of T cells and natural killers. Additionally, melatonin has an immunomodulatory impact; in hamsters exposed to a chemical carcinogen, it increases CD4+ and TNF-α accumulation while decreasing eosinophils, Th17 cells, and Foxp3 expression [3].

According to clinical research, melatonin increases the effectiveness of chemotherapy, reduces adverse effects, and raises life expectancy and quality of life. These better results are thought to be a result of melatonin's antioxidant properties and ability to scavenge free radicals. For melatonin to be utilized as a preventive and therapeutically significant adjuvant to chemotherapy, more research, including in vivo animal tests and human trials, is required. There is also a need for clarification on melatonin's dose, side effects, and modalities of action.

Research suggests that melatonin may help treat diffuse solid tumors when used in conjunction with anticancer medications. When melatonin is used with chemotherapy, a meta-analysis of 21 clinical studies shows a substantial reduction in one-year mortality, better outcomes of stable illness, partial response, and complete response. Melatonin also lessens the negative effects of chemotherapy, including asthenia, thrombocytopenia, leucopenia, nausea, vomiting, and hypotension. To validate these results, nevertheless, well-designed, independently performed experiments are required [5].

Melatonin's potential advantages were investigated in research comprising 1440 individuals with late-stage solid tumors, including 279 patients with colorectal cancer (CRC), beyond standard care. Melatonin was given to half of the patients in the early phase in addition to their usual supportive treatment. Then, 200 patients with chemotherapy-resistant diffuse tumors—25 of them had colorectal cancer (CRC)—were given 20 mg of melatonin daily in the evening in addition to 5-fluorouracil with folinic acid or raltitrexed treatment.

According to the study, melatonin may be used as a preventative measure to lessen the symptoms of advanced cancer, such as cachexia, asthenia, and lymphocytopenia, as well as the side effects of medication, such as asthenia, thrombocytopenia, and cardiac and brain toxicity. The study also demonstrated the mutually beneficial interactions between melatonin and anti-tumor drugs. This implies that melatonin may have a function in treating late-stage solid tumors, such as colorectal cancer, by reducing symptoms and improving treatment outcomes