Melatonin and 5-fluorouracil combination chemotherapy: opportunities and efficacy in cancer therapy

Abstract

Combined chemotherapy is a treatment method based on the simultaneous use of two or more therapeutic agents; it is frequently necessary to produce a more effective treatment for cancer patients. Such combined treatments often improve the outcomes over that of the monotherapy approach, as the drugs synergistically target critical cell signaling pathways or work independently at different oncostatic sites. A better prognosis has been reported in patients treated with combination therapy than in patients treated with single drug chemotherapy. In recent decades, 5-fluorouracil (5-FU) has become one of the most widely used chemotherapy agents in cancer treatment. This medication, which is soluble in water, is used as the first line of anti-neoplastic agent in the treatment of several cancer types including breast, head and neck, stomach and colon cancer. Within the last three decades, many studies have investigated melatonin as an anti-cancer agent; this molecule exhibits various functions in controlling the behavior of cancer cells, such as inhibiting cell growth, inducing apoptosis, and inhibiting invasion. The aim of this review is to comprehensively evaluate the role of melatonin as a complementary agent with 5-FU-based chemotherapy for cancers. Additionally, we identify the potential common signaling pathways by which melatonin and 5-FU interact to enhance the efficacy of the combined therapy. Graphic abstract

ZNF746 plays cardinal roles on colorectal cancer (CRC) cell invasion and migration and regulates mitochondrial dynamics and morphological changes of CRC cells—Role of combined melatonin and 5‐FU regimen

“…Mel and 5‐fluorouracil (5‐FU) combination chemotherapy has been recommended as an efficacious alternative in cancer therapy 36 . To verify this concept, we conducted a flow cytometric analysis to evaluate this combined regimen on CRC apoptosis.…”

“…Mel and 5-fluorouracil (5-FU) combination chemotherapy has been recommended as an efficacious alternative in cancer therapy. 36 To verify this concept, we conducted a flow cytometric analysis to evaluate this combined regimen on CRC apoptosis. The result showed that as compared with the control group, the total apoptosis of HCT116 and DLD-1 cell lines were significantly increased in Mel or 5-FU treatment and further significantly increased in the combined regimen of Mel + 5-FU regardless of shLacZ, shZNF746, and ZNF746, implicating that combination of Mel + F-5U has therapeutic potential for those advanced CRC, especially when the advanced CRC patients are refractory to conventional therapy (Figure 4).…”

MFAE: Multilevel Feature Aggregation Enhanced Drug‐Target Affinity Prediction for Drug Repurposing Against Colorectal Cancer

“…where T ∈ ℝ GÂP is the vector of group statistics, and t g;p is an element of T. Next, we normalize the input feature maps using the group statistics T t g;p ¼ t g;p À μ g σ g (7) where μ g and σ g are the mean and standard deviation of features in group g across spatial positions, respectively. The normalized value t g;p is then scaled and shifted element-wise by learned parameters w g and b g…”

“…Currently, chemotherapy drugs such as 5-fluorouracil (5-FU) combined with platinum-based drugs are the standard first-line treatment for advanced CRC. [7,8] However, these drugs have significant toxicity, and tumor cells can easily develop resistance. [9] In recent years, immune checkpoint inhibitors have also been introduced for the treatment of CRC, but their efficacy is still limited, benefiting only 10-30% of patients.…”

Role of Melatonin in Viral, Bacterial and Parasitic Infections

“…In BM, hematopoietic stem and progenitors cells’ (HSPCs) circadian mobilization and circulation are essential for replenishing the blood with immunocompetent cells and ensuring the immune system’s homeostasis. In this process, BM-derived MLT plays a major role by inducing HSPC quiescence and retention [ 55 ].…”