Type of malignancy | Melatonin dose/concentration | Angiogenesis-related targets | Key findings | Model | Cell line | Refs. |
---|---|---|---|---|---|---|
Breast cancer | 1 mM | VEGF, ANG-1, ANG-2 | Downregulated angiopoietins with a decrease in VEGF | In vitro | MCF-7 | [125] |
Dalton's lymphoma | 1 and 5 mM | VEGF, FGF, TIMP3 | Decreased the Dalton’s lymphoma ascites–mediated angiogenesis | In vivo, in vitro | A549 and SiHa | [126] |
serous papillary ovarian cancer | 200 µg/100 g b.w | VEGF, HIF-1α | Significantly decreased angiogenesis-associated markers, ovarian cancer size and microvessel density | In vivo | - | [127] |
canine mammary tumor cells | 1Â mM | VEGF | Decreased cell viability, enhanced caspase-3 cleaved and proteins implicated in the apoptotic pathway and diminished pro-angiogenic VEGFA | In vitro | CF-41, CMT-U229 | [128] |
Neuroblastoma | 1Â mM or 1Â nM | VEGF | Inhibited proliferation and migration of cancer cells | In vitro | SH-SY5Y | [129] |
Gastric cancer | 3 mM 100, 150 mg/kg | VEGF, HIF-1α, RZR/RORγ, SENP1 | Suppressed gastric cancer growth and blockaded tumor angiogenesis Decreased the expression of melatonin nuclear receptor RZR/RORγ | In vitro, in vivo | SGC-7901 | [130] |
Breast cancer | 1Â mM | - | Regulated inflammation Decreased cancer cell viability and cancer associated fibroblasts | In vitro | MDA-MB-231 | [52] |
Breast cancer | 1 mM | HIF-1α, VEGF, EGFR, angiogenin, | Reduced protein and gene expression of angiogenesis markers and also decreased cancer cell viability | In vitro | MCF-7, MDA-MB-231 | [131] |
Breast cancer | 10Â mg/kg | VEGF | The combination of melatonin and P. acnes cured forty percent of treated mice, suppressed metastasisand decreased angiogenesis and mediated apoptosis | In vivo | EMT6/P | [132] |
Prostate cancer | 1 mM | HIF-1α, VEGF | Upregulationn of miRNA374b and miRNA3195 mediated melatonin-induced anti-angiogenic properties | In vitro | PC-3 | [133] |
Oral cancer | 1 mM | HIF-1α, VEGF | Decreased cancer cell viability, inhibited metastasis and angiogenesis | In vitro | SCC9, SCC25 | [51] |
Hepatocellular carcinoma | 1 mM | VEGF, HIF-1α, STAT3 | Melatonin exerted its anti-angiogenic effects through interfering with the transcriptional activation of mentioned markers | In vitro | HepG2 | [134] |
Breast cancer | 1Â mM | VEGF | Inhibited stimulatory impacts on the proliferation of human umbilical vein endothelial cells (HUVECs) as well as VEGF protein levels | In vitro | MCF-7 | [46] |
Renal cancer | 20 mg/kg 10 µM | HIF-1α | Inhibited tumor growth, blocked tumor angiogenesis and diminished HIF-1α protein expression within the tumor mass during tumorigenesis | In vivo, in vivo | RENCA | [135] |
Breast cancer | 1Â mM 40Â mg/kg | VEGFR2, micro-vessel density (MVD) | Inhibited tumor growth and proliferation | In vivo, in vitro | MDA-MB-231 | [136] |
Colon cancer | 1 mM | VEGF, HIF-1α | Suppressed invasion and migration | In vitro | HCT116 | [44] |
Breast cancer | 40 mg 0.001 mM, 0.01 mM, 0.1 mM and 1 mM | VEGF, IGF-IR, HIF-1α | Increased miR-152-3p expression leading to suppress breast cancer | In vitro | MDA-MB-468 | [137] |
Breast cancer | - | IGF-1R, VEGF | Inhibited survival, migration and invasion of breast cancer cells Increased the gene level of miR-148a-3p | In vivo, in vitro | MDA-MB-231 | [138] |
Advanced cancer patients (CRC, HCC, RCC, NSCLC) | 20Â mg | VEGF | Controlled tumor growth by anti-angiogenic roles | Human | - | [54] |