Table 2.
Phytochemicals and their target miRNAs regulating tumor angiogenesis.
| Compound | Target miRNA | Effects | Cells | References | |
|---|---|---|---|---|---|
| 1 | Cardamonin (50 μM) |
↓miRNA-21 | ↓VEGF mediated angiogenesis, inhibits EC proliferation and migration | HUVECs | [114] |
| 2 | Resveratrol (50 μM) |
miRNA-34a miRNA-424 miRNA-503 ↓miR-155 ↑miRNA-21 ↑miR129 and miR489 ↑miR-141 and miR-200c |
↓VEGF-↓glycolytic genes, ↓ERK 1/2, ↓NO ↓IL-8/CXCL8 ↓DNMT1, DNMT3b ↓Stemness |
HUVEC, Estrogen dependent mammary carcinoma rat model MDA-MB-231 |
[117,123,143,144] |
| 3 | Silibinin (in combination with EGCG) (91.22 μM and 68.07 μM) |
↓miRNA-21 ↓miR-17−92 |
↑CASP-9 and APAF-1 ↓VEGF−VEGFR2 axis |
T47D, HUVEC |
[145] |
| 4 | Curcumin (30–60 lmol l−1) |
miRNA-29 ↓miRNA-21 ↑miR-15a and miR-16 |
PDCD4, PTEN/PI3K/AKT and NF-κB ↓Bcl-2 Pro- or anti-angiogenic at different concentrations |
MCF-7 | [146,147,148] |
| 5 | Metformin (anti-diabetic drug) (20 mM) |
↓miRNA-21 ↓miRNA-221 miRNA-34a ↑miRNA-26a ↓Let-7a |
Anti-angiogenic via ↓TGF-β, PTEN, EHZ2 and SMAD7 eNOS signalling |
HUVECs MDA-MB-231, MDA-MB-468, BT 549, MCF-7 |
[75,91,101,149,150,151] |
| 6 | Genistein (10–25 μM) |
↓miRNA-155 ↑miRNA-23b ↓miRNA 221/222 |
↑FOXO3, PTEN Regulates viability and apoptosis via transcriptional regulation of miR-155 ↓Metastasis, enhances focal adhesion connections |
MDA-MB-435, Hs578t | [127,152] |
| 7 | EGCG (20 µM) |
↓pro angiogenic ↑anti angiogenic miRNA ↓miRNA 27a ↓miRNA-21 |
↓HIF1α, GLUT1 ↓HK, PFK, LDH (glycolytic enzymes) ZBTB10 |
4T1, MCF-7 |
[126] [116,153] |
| 8 | Luteolin (50 µmol/L) |
↓miRNA-155 ↓miRNA-21 ↑miR-34a ↑miRNA-181a, ↑miRNA-139-5p ↑miRNA-224 and ↑miRNA-246 ↑miRNA-203 |
↓Notch signaling, ↓PI3K/Akt, ↓VEGF, ↓Notch-1, ↓Hes-1, ↓Hey, ↓VEGF, ↓Cyclin D1 and MMP2/9 ↓Tumor growth, ↓Invasion ↓Angiogenesis Anti-oxidant |
MDA-MB-231, HUVECs |
[154,155,156] |
| 9 | Sinomenine (4 µM) |
↑miRNA-29 | miR-29/PDCD-4 axis ↓Tumor growth, ↓Metastasis, invasion, vascular normalization, improved tumor immunity |
HUVEC 4T1(murine breast cancer model) MDA-MB-231, MCF-7 |
[157,158] |
| 10 | Triptolide (15 ng/mL) |
↑miRNA-146a | ↓Rho GTPase - ↓Metastasis and invasion ↓ERK1/2-/HIF-1α/6666VEGFA axis |
MDA-MB-231 | [132,159] |
| 11 | Betulinic acid (2.5–10 μmMol/L) |
↓miRNA-27a | ↑ZBTB10 and Myt-1 | MDA-MB-231, BT-549 | [124] |