Table 2.
Antimetastatic effects of pomegranate determined in in vitro and in vivo pre-clinical studies
| Cancer type | Studied Model | In vitro / in vivo /clinical | Extract/Phytochemical | Mechanism | Ref |
|---|---|---|---|---|---|
| Bladder | T24 | In vitro | Extract (juice) | Inactivated PTEN/AKT/mTORC1 pathway via profilin 1 up-regulation | [42] |
| Breast | MDA-MB-231 | In vitro | Extract (peel) | Decreased expression of β-catenin & EMT markers | [52] |
| MDA-MB-231 | In vitro | Extract (peel) | Down-regulation of metastasis-related genes | [53] | |
| MDA-MB-231, MCF-7 | In vitro | Extract (seed oil) | Reduced secretion of inflammatory cytokines | [54] | |
| MDA-MB-231, MCF-7 | In vitro | Juice or a combination of luteolin+ellagic acid+punicic acid | Reduced expression of pro-inflammatory cytokines/chemokines, adhesion molecules, cytoskeletal & ECM proteins, &EMT markers | [55] | |
| MDA-MB-231, MCF-7, MCF-10A | In vitro | Extract (seed oil), Fermented juice | Reduced expression of VEGF, inhibited angiogenesis | [56] | |
| Colon | HT-29, AOM-induced ACF rats | In vitro, in vivo | Juice | Targeting miR-126-regulated pathways which contribute in anti-inflammatory & anti-angiogenic mechanisms |
[45] |
| HT-29 | In vitro | Juice, Tannin, Punicalagin | Abolish TNFα-induced AKT activation resulting modulation of inflammatory cell signaling | [57] | |
| Liver | DENA induced-rat hepatocarcinoma | In vivo | Emulsion | Suppression of the inflammatory cascade through modulation of NF- κB signaling pathway |
[47] |
| Lung | A549, H1299, LL/2 | In vitro | Extract (leaves) | Reduction of MMP-2 & MMP-9 expression | [48] |
| A549 | In vitro | Galactomannan (PSP001) isolated from the fruit rind | Down-regulation of VEGF & MMPs | [58] | |
| Ovarian | A2780, ES-2 in nude mice | In vitro, in vivo | Fruit juice, Ellagic acid, Luteolin | Decreased expression of MMP2 & MMP9 | [49] |
| A2780 | In vitro | Punicalagin | Suppression of MMPs acitivities | [59] | |
| Prostate | LNCaP, LAPC4, CL1, DU145, LAPC4 in SCID mice | In vitro, in vivo | Extract | NF-κB blockade | [60] |
| LNCaP, HUVEC, LAPC4 in SCID mice | In vitro, in vivo | Extract | Decreased expression of HIF-1α &VEGF | [ 61 ] | |
| DU145, PC3, LNCaP | In vitro | Luteolin+Ellagic acid+ Punicic acid | Decreased expression of oncogenic miRNAs & inhibition of the CXCR4/SDF1α chemotaxis axis, changes in the expression of cell adhesion & cytoskeletal proteins | [62] | |
| PC-3, PLS10 | In vitro | Ellagic acid | Decreased secretion of MMP-2, inhibited collagenase IV activity | [63] | |
| DU145, PC3, TRAMP-C1 | In vitro | Extract (peel) | Down-regulation of MMPs | [64] | |
| PC3 | In vitro | Ellagic acid, Caffeic acid, Luteolin, Punicic acid | - | [65] | |
| PC3 | In vitro | Extracts (peel, juice, seeds) | Decreased expression of PLA2 | [66] | |
| Renal | ACHN, SN12C | In vitro | Extract (juice) | Inhibition of NF-kB and JNK pathways, consequently inhibition of EMT phenotype | [67] |
| Skin | A375, B16F10 in C57BL/6 mice | In vitro, in vivo | Galactomannan (PSP001) isolated from the fruit rind | Down-regulation of VEGF & MMPs | [58] |
CXCR4: C-X-C chemokine receptor type 4; ECM: Extracellular matrix; EMT: Epithelial mesenchymal transition; ERK: Extracellular signal-regulated kinase; HIF-1: Hypoxia-inducible factor 1; JNK: Jun N-terminal kinases; MMP: Matrix metalloproteinase; miRNA: microRNA; mTOR: Mammalian target of rapamycin; NF-κB: Nuclear factor-κB; PLA2: Phospholipases A2; PTEN: Phosphatase and tensin homolog; SCID: Severe combined immunodeficient; SDF1: Stromal cell-derived factor 1; TNF-α: Tumor necrosis factor-α; VEGF: Vascular endothelial growth factor.