| Properties | Information | |
|---|---|---|
| PhytoCAT-ID | PhytoCAT-1136 | |
| Phytochemical name or plant extracts | Honokiol | |
| PMID | 19135778 | |
| Literature evidence | In this study, we evaluated the growth inhibitory activity of honokiol in cultured estrogen receptor (ER)-negative MDA-MB-231 human breast cancer cells. | |
| IUPAC name | 2-(4-hydroxy-3-prop-2-enylphenyl)-4-prop-2-enylphenol | |
| Phytochemicals’ class or type of plant extracts | Neolignan | |
| Source of phytochemicals or plant Extracts | Magnolia obovata | |
| Geographical availability | Japan, Kuril Is. | |
| Plant parts | Bark | |
| Other cancers | Breast cancer | |
| Target gene or protein | c-Src, EGFR, AKT, mTOR , 4E-BP and p70 S6 kinase, Caspase 3, Caspase 8, Caspase 9, Bid, Bcl-2, Neu1, NO, COX-2, NF-kB, IL-6, miR-188-5p, FBXW7 | |
| Gene or Protein evidence | In the analysis of signal transduction pathway, honokiol down-regulated the expression and phosphorylation of c-Src, epidermal growth factor receptor (EGFR), and Akt, and consequently led to the inactivation of mTOR and its downstream signal molecules including 4E-binding protein (4E-BP) and p70 S6 kinase. Apoptosis caused by honokiol was also concomitant with the cleavage of caspases (caspase-3, -8, and -9) and Bid along with the suppressive expression of Bcl-2, but it was independent on the expression of Bax and p53. Additional observations indicated that the phytochemical, honokiol downregulates the expression of Neu1. These results indicate that NO and COX-2 are the key targets of honokiol in the inhibition of breast cancer cell migration, an essential step in invasion and metastasis. Moreover, honokiol inhibited the activation of nuclear factor kB (NF-kB), an upstream regulator of COX-2 and iNOS, in 4T1 cells. Anti-cancer effect of honokiol was demonstrated with the decrease in the release of cytokine IL-6 and further suppression of Ki-67 proliferative protein. These findings suggest that downregulation of miR-188-5p by honokiol enhances doxorubicin sensitivity through FBXW7/c-Myc signaling in human breast cancer. However, FBXW7 silencing or c-Myc transfection resulted in resistance to the honokiol-induced apoptotic effect. | |
| Target pathways | Honokiol antagonizes doxorubicin resistance in human breast cancer via miR-188-5p/FBXW7/c-Myc pathway. Down-regulation of c-Src/EGFR-mediated signaling activation is involved in the honokiol-induced cell cycle arrest and apoptosis in MDA-MB-231 human breast cancer cells | |
| IC50 | NA | |
| Potency | HNK exhibited potent anti-proliferative activity against breast cancer cell lines and enhanced the activity of other drugs used for the treatment of breast cancer. | |
| Cell line/ mice model | Female Sprague Dawlely (SD) rats, MCF-7/ADR, MCF-7, 4T1, MDA-MB-231 | |
| Additional information | Here, we show that honokiol down-regulated the expression of P-glycoprotein at mRNA and protein levels in MCF-7/ADR, a human breast MDR cancer cell line. These findings suggest that downregulation of miR-188-5p by honokiol enhances doxorubicin sensitivity through FBXW7/c-Myc signaling in human breast cancer. Our study finds an important role of miR-188-5p in the development of doxorubicin resistance in breast cancer, and enriches our understanding of the mechanism of action of honokiol in cancer therapy. | |
| PubChem ID | 72303 | |
| Additional PMIDs | 30690424 33544209 25442261 30259402 21225228 31515676 28620301 16406853 19135778 34426156 32263837 33399110 17487375 | |
| Additional sources of information | https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:554784-1 | |
| Safety | NA |