| Properties | Information | |
|---|---|---|
| PhytoCAT-ID | PhytoCAT-1868 | |
| Phytochemical name or plant extracts | Shikonin | |
| PMID | 26496737 | |
| Literature evidence | RIP1K and RIP3K provoked by shikonin induce cell cycle arrest in the triple negative breast cancer cell line, MDA-MB-468: necroptosis as a desperate programmed suicide pathway. | |
| IUPAC name | 5,8-dihydroxy-2-[(1R)-1-hydroxy-4-methylpent-3-enyl]naphthalene-1,4-dione | |
| Phytochemicals’ class or type of plant extracts | Quinone | |
| Source of phytochemicals or plant Extracts | Lithospermum erythrorhizon | |
| Geographical availability | Amur, China North-Central, China South-Central, China Southeast, Chita, Inner Mongolia, Japan, Korea, Manchuria, Primorye, Yakutskiya | |
| Plant parts | Root | |
| Other cancers | Breast cancer | |
| Target gene or protein | DUSP1, DUSP2, ERα, GPER, EGFR, p-ERK, RIP1K, RIP3K, E-cadherin, N-cadherin, vimentin, Snail | |
| Gene or Protein evidence | Therefore, our results suggest that shikonin induces the expression of DUSP1 and DUSP2 which consequently switches off JNK and p38 MAPK pathways and causes cell cycle arrest and apoptosis in breast cancer cells. Furthermore, shikonin downregulated the expression of ERα and GPER, and this effect was not affected by the estrogen environment. In addition, shikonin downregulated the EGFR and p-ERK expression in MCF-7 and SK-BR-3, which was also not affected by the estrogen environment. RIP1K and RIP3K provoked by shikonin induce cell cycle arrest in the triple negative breast cancer cell line, MDA-MB-468: necroptosis as a desperate programmed suicide pathway. Shikonin depressed cell migration and invasion, upregulated E-cadherin levels, downregulated N-cadherin, vimentin, and Snail levels, and reorganized the cytoskeletal proteins F-actin and vimentin. | |
| Target pathways | GSK-3β-regulated suppression of β-catenin signaling. JNK and p38 MAPK pathways | |
| IC50 | 10.3 μΜ against MCF-7 15.0 μΜ against SKBR-3 15.0 μΜ against MDA-MB-231 | |
| Potency | the results revealed that shikonin potently decreased the viabilities of TNBC MDA-MB-231 and 4T1 cells but showed less cytotoxicity to normal mammary epithelial MCF-12A cells. | |
| Cell line/ mice model | MDA-MB-468, MDA-MB-231, MCF-7, SKBR-3 | |
| Additional information | An increase in the ROS levels and a reduction in mitochondrial membrane potential have been observed in the shikonin-treated cells. Cell death has mainly occurred through necroptosis with a significant increase in the RIP1K and RIP3K expressions, and characteristic morphological changes have been observed. In the presence of Nec-1, caspase-3 mediating apoptosis has occurred in the shikonin-treated cells. | |
| PubChem ID | 479503 | |
| Additional PMIDs | 31071331 29422643 31545985 | |
| Additional sources of information | https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:118039-1 | |
| Safety | NA |