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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]