Table 1 Melatonin enhancement the antitumor activity of 5-FU chemotherapy
From: Melatonin and 5-fluorouracil combination chemotherapy: opportunities and efficacy in cancer therapy
Cancer Type | Model | Sample type | Dose of Melatonin | Signaling pathway | Findings | References |
|---|---|---|---|---|---|---|
Pancreatic cancer | In vitro | AR42J cells | 1 mM | – | Promotion the depolarization of mitochondrial membrane and ROS generation in cancer cells ↑ Apoptosis in cancer cells | [85] |
Colon cancer | In vitro In vivo | SW620 and LOVO cells Female athymic nude mice | 1 mM 25 mg/kg | PI3K/Akt signaling NF-κB/iNOS signaling | Suppress of proliferation, migration, invasion and colony formation in colon cancer cells Induce the activation of apoptosis via caspase/PARP- dependent pathway Promote cell cycle arrest | [120] |
Oesophageal squamous cell carcinoma | In vitro In vivo | KYSE520, KYSE410, KYSE150, KYSE30 cells Female BABL/c nude mice | Range of 0–5 mM 25 mg/kg | Suppression of Erk and Akt pathway | Inhibition proliferation, migration, invasion and promotion apoptosis (mitochondria-dependent) of ESCC cells in vitro Inhibition tumor growth in mice model ↑ Effectively cytotoxicity of 5-Fu to ESCC in vitro and in vivo Inhibition the phosphorylation of Erk and Akt | [136] |
Colorectal cancer Cervical cancer | In vitro | HT-29 cell line HeLa cell line | 1 mM | Promotion of MT3 melatonin receptors | ↑ chemotherapeutic-induced apoptosis and cytotoxicity in tumor cell lines | [146] |
Colon cancer | Human In vitro In vivo | Colorectal cancer specimens SNU-C5/WT, SNU-C5/5FUR, SNU-C5/Oxal, S707 cells Xenograft models mice | – | Regulation of PrPC and Oct4 axis | Inhibition the colorectal cancer cell proliferation and development via promoting autophagy and apoptosis | [147] |
Colorectal cancer | In vitro | HT29 cell line | 1 mM | N/D | ↑ Cytotoxic effects of 5-FU ↑ Sensitivity of cell line to treatment with 5-FU ↑ Ratio of cells that overproduce intracellular ROS and significantly increased the population of apoptotic cells | [113] |
Anastomotic leakage | In vivo | Male Wistar rats | 0.4 mg/kg | N/D | ** ↓ Inflammation and necrosis formation ↓ TNF-α and IL-1β plasma levels | [166] |
Colorectal cancer | Human In vitro | Cancer tissues HCT116, SW480, COLO320, DLD-1, HT29, RKO, CaCO2 and SW620 cells | Different dosage (1–4 mM) | Upregulation of miR-215-5p / simultaneously downregulation of TYMS | Inhibition the cell growth Induction apoptosis ↑ Cytotoxic effects of 5-FU in 5-FU resistant cells | [169] |
Esophageal cancer | In vitro | EC-9706 and EC-109 and HET-1A cells | 0–2 mM | Regulating EZH2 expression | Inhibition of cell proliferation Promotion of apoptosis Inhibition of invasion and migration in EC-9706 and EC-109 cells | [195] |
Colorectal cancer | In vitro | SW-480 cell lines | 75, 150, 200 µM | Increasing OS and targeting XIAP and surviving | ↓ Cell proliferation ↑ Intracellular levels of ROS and Inhibition the activity of antioxidant enzymatic Reversing effect on the resistance to apoptosis and augmented the cytotoxicity of 5-FU | [97] |