| Properties | Information | |
|---|---|---|
| PhytoCAT-ID | PhytoCAT-1 | |
| Phytochemical name or plant extracts | Limonin | |
| PMID | 35117291 | |
| Literature evidence | The Wound-healing and Transwell chamber invasion assays were used to detect the inhibition effect of limonin on migration and invasion of HUVECs cells or breast cancer cells. | |
| IUPAC name | (1R,2R,7S,10R,13R,14R,16S,19S,20S)-19-(furan-3-yl)-9,9,13,20-tetramethyl-4,8,15,18-tetraoxahexacyclo[11.9.0.02,7.02,10.014,16.014,20]docosane-5,12,17-trione | |
| Phytochemicals’ class or type of plant extracts | Triterpenoid | |
| Source of phytochemicals or plant Extracts | Citrus limetta | |
| Geographical availability | India | |
| Plant parts | Seeds | |
| Other cancers | Breast cancer | |
| Target gene or protein | VEGF, VEGFR2, STAT3, MMP9, miR-216a-3p, ABCG2 | |
| Gene or Protein evidence | Limonin dose-dependently inhibited the vascular endothelial growth factor (VEGF)-mediated tyrosine phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2) by blocking VEGF binding to VEGFR2 and suppressing constitutive STAT3 activation in human umbilical vein endothelial cells. Limonin effectively inhibited VEGF-induced endothelial cell proliferation, migration and tubular-structure formation in vitro and markedly reduced VEGF-triggered neovascularization in mouse matrigel plugs in vivo. Moreover, limonin treatment led to a remarkable suppression of tumor metastasis by decreasing the phosphorylation of insulin growth factor receptor 1-mediated STAT3 and the expression levels of its downstream members MMP-9 and VEGF in breast cancer cells. The data further showed that limonin increased the levels of the negative STAT3 regulator SHP-1 in breast cancer cells. Mechanistically, limonin decreased MIR216A methylation level and thus increased miR-216a-3p expression. Of the non-flavonoid phytochemicals tested, berberine, celastrol, ellagic acid, limonin, oleanolic acid, propyl gallate, sinapic acid and ursolic acid demonstrated significant inhibition of ABCG2-mediated transport. | |
| Target pathways | miR-216a-3p/Wnt/β-catenin signaling VEGFR2/IGFR1-mediated STAT3 signaling pathway | |
| IC50 | limonin + adriamycin = 7.4 µM against MCF-Adr | |
| Potency | Mechanistically, limonin decreased MIR216A methylation level and thus increased miR-216a-3p expression. Furthermore, miR-216a-3p could directly bind to WNT3A and thus inactivated Wnt/β-catenin pathway. Therefore, our results indicate that limonin could attenuate the stemness and chemoresistance via inhibiting MIR216A methylation and subsequently suppressing Wnt/β-catenin pathway. | |
| Cell line/ mice model | MCF-7-Adr, MDA-MB-231, MCF-7 | |
| Additional information | Limonin is a promising anti-angiogenic and anti-metastatic candidate compound that can be further optimized as a therapeutic agent for breast cancer. | |
| PubChem ID | 179651 | |
| Additional PMIDs | 23497885 30717533 23117440 28425165 | |
| Additional sources of information | https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:60454758-2 | |
| Safety | Here, we found that limonin attenuated the stemness of breast cancer cells in a concentration-dependent manner, evident by the decreasing the capacity of cell spheroid formation, expression of stemness markers and ALDH1 activity, whereas had no toxicity on non-tumorigenic cells. |