| Properties | Information | |
|---|---|---|
| PhytoCAT-ID | PhytoCAT-587 | |
| Phytochemical name or plant extracts | Toosendanin (TSN) | |
| PMID | 29574068 | |
| Literature evidence | Natural product toosendanin reverses the resistance of human breast cancer cells to adriamycin as a novel PI3K inhibitor. | |
| IUPAC name | [(1S,2R,4R,5R,6S,8R,10S,11S,12R,14R,15R,16R,19S,21R)-4-acetyloxy-6-(furan-3-yl)-12,16,19-trihydroxy-5,11,15-trimethyl-3-oxo-9,17-dioxahexacyclo[13.3.3.01,14.02,11.05,10.08,10]henicosan-21-yl] acetate | |
| Phytochemicals’ class or type of plant extracts | Triterpenoid | |
| Source of phytochemicals or plant Extracts | Melia azedarach | |
| Geographical availability | Assam, Bangladesh, Cambodia, China North-Central, China South-Central, China Southeast, East Himalaya, Hainan, India, Jawa, Laos, Lesser Sunda Is., Nepal, New Guinea, New South Wales, Northern Territory, Philippines, Queensland, Solomon Is., Sri Lanka, Sumatera, Taiwan, Thailand, Vietnam, West Himalaya, Western Australia | |
| Plant parts | Bark | |
| Other cancers | Breast cancer | |
| Target gene or protein | ABCB1, PI3K P110α, P110β, Procaspase 3, Procaspase 9, Bcl-xL, LC3B, Beclin-1, PI3K | |
| Gene or Protein evidence | Furthermore, TSN could significantly reduce ABCB1 expression. Importantly, the inhibitory effect of TSN on PI3K P110α and P110β expression was specifically observed in breast cancer cells but not in normal human cells. Moreover, TSN (20 nM) and ITSN (2.5 μM) induced the cleavage of pro-caspase-3 and pro-caspase-9, and decreased the expression of anti-apoptotic Bcl-xL in both MDA-MB-231 and 4T1 cells. Results from scanning electron microscope observation and detecting the expression of microtubule-associated protein 1 light chain 3B (LC3B) and Beclin 1 evidenced that TSN (20 nM) and ITSN (2.5 μM) induced autophagy in both MDA-MB-231 and 4T1 cells. Thus, TSN could be used as a novel PI3K inhibitor to reverse breast cancer resistance. | |
| Target pathways | NA | |
| IC50 | NA | |
| Potency | Thus, TSN could be used as a novel PI3K inhibitor to reverse breast cancer resistance. The combination of ADM and TSN may represent a useful strategy for human breast cancer therapy. Collectively, this study shows that natural compound TSN and ITSN suppress TNBC growth via inducing necrosis, apoptosis and autophagy. TSN and ITSN could be promising drugs for TNBC treatment. | |
| Cell line/ mice model | MDA-MB-231, BT-549, 4T1 xenograft tumor | |
| Additional information | We then found that TSN was capable of suppressing adriamycin-induced Akt phosphorylation, probably due to downregulation of the PI3K catalytic subunits P110α and P110β, and inhibition of DNA-PKcs. Results from scanning electron microscope observation and detecting the expression of microtubule-associated protein 1 light chain 3B (LC3B) and Beclin 1 evidenced that TSN (20 nM) and ITSN (2.5 μM) induced autophagy in both MDA-MB-231 and 4T1 cells. | |
| PubChem ID | 9851101 | |
| Additional PMIDs | 34742683 | |
| Additional sources of information | https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:578949-1 | |
| Safety | TSN and ITSN decreased 4T1 xenograft tumor growth without inflicting toxicity on vital organs in mice. |