| Properties | Information | |
|---|---|---|
| PhytoCAT-ID | PhytoCAT-2019 | |
| Phytochemical name or plant extracts | β-elemene | |
| PMID | 25562151 | |
| Literature evidence | BACKGROUND: Multidrug resistance (MDR) directly contributes to the clinical failure of chemotherapy in breast cancer (BCA). β-elemene is a natural antitumor drug from plants. | |
| IUPAC name | (1S,2S,4R)-1-ethenyl-1-methyl-2,4-bis(prop-1-en-2-yl)cyclohexane | |
| Phytochemicals’ class or type of plant extracts | Sesquiterpenoid | |
| Source of phytochemicals or plant Extracts | Zanthoxylum setulosum | |
| Geographical availability | Colombia, Costa Rica, Nicaragua, Panamá, Venezuela | |
| Plant parts | Leaves oil | |
| Other cancers | Breast cancer | |
| Target gene or protein | SNAI1, SNAI2, TWIST, SIP1, TGF-β1, Smad3, EGFR, GLUT1, LDHA, PKM-2, importin α5, PTEN, Pgp, PKM2, EMT | |
| Gene or Protein evidence | We found that ELE (40 µg/ml ) blocked the TGF-β1-induced phenotypic transition in the human breast cancer cell line MCF-7. ELE was able to inhibit TGF-β1-mediated upregulation of mRNA and protein expression of nuclear transcription factors (SNAI1, SNAI2, TWIST and SIP1), potentially through decreasing the expression and phosphorylation of Smad3, a central protein mediating the TGF-β1 signalling pathway. Further analysis revealed that β-elemene suppressed aerobic glycolysis by blocking PKM2 nuclear translocation and the expression of EGFR, GLUT1 and LDHA by influencing the expression of importin α5. The PTEN expression under intervention of β-elemene was significantly increased and Pgp expression under β-elemene intervention was significantly decreased in both cell lines. Here, we found a tight relationship between PKM2 and breast cancer metastasis, demonstrated by the findings that beta-elemene (β-elemene), an approved drug for complementary cancer therapy, exerted distinct anti-metastatic activity dependent on PKM2. In the present study, we investigated the inhibitory effect of beta-elemene (ELE), an active component of a natural plant-derived anti-neoplastic agent in an established EMT model mediated by transforming growth factor-beta1 (TGF-β1). | |
| Target pathways | TGF-β1 signalling pathway | |
| IC50 | The IC50 for ELE was 534 µg/ml in TGF-β1-treated MCF-7 cells and 275 µg/ml in control cells, respectively. | |
| Potency | β-elemene could influence MDR related miRNA expression and subsequently regulate the expression of the target genes PTEN and Pgp, which may lead to reduction of the viability of the chemo-resistant breast cancer cells. These findings suggest a potential therapeutic benefit of ELE in treating basal-like breast cancer. Taken together, tetrameric transformation and nuclear translocation of PKM2 are essential for cancer metastasis, and β-elemene inhibited breast cancer metastasis via blocking aerobic glycolysis mediated by dimeric PKM2 transformation and nuclear translocation, being a promising anti-metastatic agent from natural compounds. | |
| Cell line/ mice model | MCF-7/Adr, MCF-7/Doc, MCF-7 | |
| Additional information | Compared with the miRNAs expression profiles of MCF-7/Adr and MCF-7/Doc cell lines from our previous studies, there were 322 differentially expressed miRNAs in MCF-7/Adr and MCF-7/Doc breast cancer cells with β-elemene intervention (50μM/L) for 30h, and 6 miRNAs were significantly up-regulated and 12 miRNAs were significantly down-regulated in both MCF-7/Adr and MCF-7/Doc. We have testified that 5 miRNA is related to MDR before, in this study, the expression of miR-34a, miR-222, miR-452 and miR-29a can lead to changes of the characteristics of chemo-resistant MCF-7/Adr and MCF-7/Doc. The results indicated that β-elemene inhibited breast cancer cell migration, invasion in vitro as well as metastases in vivo. β-Elemene further inhibited the process of aerobic glycolysis and decreased the utilization of glucose and the production of pyruvate and lactate through suppressing pyruvate kinase activity by modulating the transformation of dimeric and tetrameric forms of PKM2. | |
| PubChem ID | 6918391 | |
| Additional PMIDs | 23516540 31343107 17999336 | |
| Additional sources of information | https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:270783-2 | |
| Safety | NA |