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Table 1 Melatonin fights against different cancers trough angiogenesis modulation

From: An updated review of mechanistic potentials of melatonin against cancer: pivotal roles in angiogenesis, apoptosis, autophagy, endoplasmic reticulum stress and oxidative stress

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 1 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 1 mM or 1 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 1 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 10 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 1 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 1 mM
40 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) 20 mg VEGF Controlled tumor growth by anti-angiogenic roles Human - [54]