Natural Product (NP) Details
| General Information of the NP (ID: NP8751) | |||||
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| Name |
Shikonin
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| Synonyms |
NSC 252844; Shikonin S; Shikonin,(S); Tokyo Violet
Click to Show/Hide
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| Species Origin | Lithospermum erythrorhizon ... | Click to Show/Hide | |||
| Lithospermum erythrorhizon | |||||
| Disease | Zoonotic viral disease [ICD-11: 1D6Y] | Investigative | [1] | ||
| Structure |
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Click to Download Mol2D MOL |
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| Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product | |||||
| Formula |
C16H16O5
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| PubChem CID | |||||
| Canonical SMILES |
CC(=CCC(C1=CC(=O)C2=C(C=CC(=C2C1=O)O)O)O)C
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| InChI |
1S/C16H16O5/c1-8(2)3-4-10(17)9-7-13(20)14-11(18)5-6-12(19)15(14)16(9)21/h3,5-7,10,17-19H,4H2,1-2H3/t10-/m1/s1
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| InChIKey |
NEZONWMXZKDMKF-SNVBAGLBSA-N
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| CAS Number |
CAS 517-89-5
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| Herb ID | |||||
| ETMC ID | |||||
| SymMap ID | |||||
| TTD Drug ID | |||||
| Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally | ||||||
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| α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP | ||||||
| Cisplatin | Bladder cancer | Click to Show/Hide the Molecular Data of This Drug | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [2] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Up-regulation | Expression | BAX | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | BCL-2 | Molecule Info |
Pathway MAP
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| Up-regulation | Activity | CASP3 | Molecule Info |
Pathway MAP
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| Up-regulation | Activity | CASP9 | Molecule Info |
Pathway MAP
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| Biological
Regulation |
Induction | ROS generation | ||||
| Induction | Loss of mitochondrial membrane potential | |||||
| In-vitro Model | HCT 116 | CVCL_0291 | Colon carcinoma | Homo sapiens | ||
| HT-29 | CVCL_0320 | Colon adenocarcinoma | Homo sapiens | |||
| SW620 | CVCL_0547 | Colon adenocarcinoma | Homo sapiens | |||
| NCM460 | CVCL_0460 | Healthy | Homo sapiens | |||
| In-vivo Model | HCT116 cells (5*106 cells in 100uL of PBS) were harvested and injected subcutaneously into the right flank of five-week-old athymic BALB/cA nu/nu female mice. | |||||
| Experimental
Result(s) |
Shikonin as a synergistic agent to cisplatin could be a highly efficient way to achieve anticancer synergism by inducing intracellular oxidative stress. | |||||
| Temozolomide | Brain cancer | Click to Show/Hide the Molecular Data of This Drug | ||||
| Augmenting Drug Sensitivity | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [3] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Down-regulation | Expression | AKT1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | MMP-2 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | MMP-9 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | SNAI2 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | VIM | Molecule Info |
Pathway MAP
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| In-vitro Model | U-118MG | CVCL_0633 | Glioma | Homo sapiens | ||
| Experimental
Result(s) |
GBM-derived cells treated with a combination of SHK and TMZ showed decreases in their proliferation and migration capacities. These decreases were followed by the suppression of GMT through a reduction of beta3 integrin, MMP-2, MMP-9, Slug and vimentin expression via inactivation of PI3K/AKT signaling. | |||||
| 4-hydroxy-tamoxifen | Cyclic Mastalgia | Click to Show/Hide the Molecular Data of This Drug | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [4] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Down-regulation | Expression | BID | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | CASP8 | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | CASP9 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | FAS | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | PIK3CB | Molecule Info |
Pathway MAP
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| Biological
Regulation |
Down-regulation | Loss of mitochondrial membrane potential | ||||
| In-vitro Model | MCF-7 | CVCL_0031 | Invasive breast carcinoma | Homo sapiens | ||
| MDA-MB-435S | CVCL_0622 | Breast cancer | Homo sapiens | |||
| In-vivo Model | Portions of the suspension (6*106 MCF-7 cells in 0.1 mL) were subcutaneously injected into the right fanks of each female nude mice. | |||||
| Experimental
Result(s) |
Shikonin and 4-hydroxytamoxifen synergistically inhibit the proliferation of breast cancer cells through activating apoptosis signaling pathway in vitro and in vivo. | |||||
| Erlotinib | Lung cancer | Click to Show/Hide the Molecular Data of This Drug | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [5] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Down-regulation | Phosphorylation | AKT1 | Molecule Info |
Pathway MAP
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| Down-regulation | Phosphorylation | EGFR | Molecule Info |
Pathway MAP
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| Down-regulation | Phosphorylation | PLCG1 | Molecule Info |
Pathway MAP
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| In-vitro Model | U-87MG ATCC | CVCL_0022 | Glioblastoma | Homo sapiens | ||
| DK-MG | CVCL_1173 | Glioblastoma | Homo sapiens | |||
| SNB-19 | CVCL_0535 | Glioblastoma | Homo sapiens | |||
| BS-153 | CVCL_S444 | Glioblastoma | Homo sapiens | |||
| A-172 | CVCL_0131 | Glioblastoma | Homo sapiens | |||
| T98G | CVCL_0556 | Glioblastoma | Homo sapiens | |||
| U-251MG | CVCL_0021 | Astrocytoma | Homo sapiens | |||
| Experimental
Result(s) |
Shikonin not only dose-dependently inhibited EGFR phosphorylation and decreased phosphorylation of EGFR downstream molecules, including AKT, P44/42MAPK and PLCgamma1, but also together with erlotinib synergistically inhibited deltaEGFR phosphorylation in U87MG. | |||||
| Gefitinib | Lung cancer | Click to Show/Hide the Molecular Data of This Drug | ||||
| Augmenting Drug Sensitivity | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [6] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Down-regulation | Expression | CCND1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | PKM | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | STAT3 | Molecule Info |
Pathway MAP
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| In-vitro Model | A-549 | CVCL_0023 | Lung adenocarcinoma | Homo sapiens | ||
| NCI-H1299 | CVCL_0060 | Lung large cell carcinoma | Homo sapiens | |||
| NCI-H1975 | CVCL_1511 | Lung adenocarcinoma | Homo sapiens | |||
| HCC827 | CVCL_2063 | Lung adenocarcinoma | Homo sapiens | |||
| In-vivo Model | Animal models were constructed by injecting A549 cells (1*107) into nude mice (six-week) in the dorsal area. | |||||
| Experimental
Result(s) |
Shikonin enhances sensitization of gefitinib against wild-type EGFR non-small cell lung cancer via inhibition PKM2/stat3/cyclinD1 signal pathway. | |||||
| Osimertinib | Lung cancer | Click to Show/Hide the Molecular Data of This Drug | ||||
| Augmenting Drug Sensitivity | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [7] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Up-regulation | Expression | ATF-4 | Molecule Info |
Pathway MAP
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| Up-regulation | Phosphorylation | EIF2S1 | Molecule Info |
Pathway MAP
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| Biological
Regulation |
Up-regulation | ROS generation | ||||
| In-vitro Model | A-549 | CVCL_0023 | Lung adenocarcinoma | Homo sapiens | ||
| NCI-H1299 | CVCL_0060 | Lung large cell carcinoma | Homo sapiens | |||
| NCI-H460 | CVCL_0459 | Lung large cell carcinoma | Homo sapiens | |||
| Experimental
Result(s) |
Shikonin increased the anticancer activity of AZD9291 in primary wtEGFR NSCLC cells through ROS-mediated ER stress. | |||||
| TNF-related apoptosis inducing ligand | Lung cancer | Click to Show/Hide the Molecular Data of This Drug | ||||
| Augmenting Drug Sensitivity | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [8] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Molecule(s)
Regulation |
Down-regulation | Phosphorylation | AKT1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | BCL-2 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | BCL-xL | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | BID | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | CASP3 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | CASP8 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | CFLAR | Molecule Info |
Pathway MAP
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| Up-regulation | Phosphorylation | JNK1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | MCL1 | Molecule Info |
Pathway MAP
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| Down-regulation | Phosphorylation | STAT3 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | XIAP | Molecule Info |
Pathway MAP
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| In-vitro Model | A-549 | CVCL_0023 | Lung adenocarcinoma | Homo sapiens | ||
| Experimental
Result(s) |
Shikonin sensitizes A549 cells to TRAIL-induced apoptosis through the JNK, STAT3 and AKT pathways. | |||||
| Doxorubicin | Solid tumour/cancer | Click to Show/Hide the Molecular Data of This Drug | ||||
| Augmenting Drug Sensitivity | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [9] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
|
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| Molecule(s)
Regulation |
Down-regulation | Phosphorylation | AKT1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | microRNA 19a | Molecule Info |
Pathway MAP
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| Down-regulation | Phosphorylation | mTOR | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | MYC | Molecule Info |
Pathway MAP
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| In-vitro Model | Raji | CVCL_0511 | EBV-related Burkitt lymphoma | Homo sapiens | ||
| Namalwa | CVCL_0067 | EBV-related Burkitt lymphoma | Homo sapiens | |||
| In-vivo Model | A mixture of 1*107 Namalwa cells and PBS was injected subcutaneously in the right oxter of each male non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice (4 weeks old). | |||||
| Experimental
Result(s) |
Shikonin exerts antitumor activity in Burkitt's lymphoma by inhibiting C-MYC and PI3K/AKT/mTOR pathway and acts synergistically with doxorubicin. | |||||
| Gemcitabine | Solid tumour/cancer | Click to Show/Hide the Molecular Data of This Drug | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [10] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
|
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| Molecule(s)
Regulation |
Down-regulation | Expression | BCL-2 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | BCL-xL | Molecule Info |
Pathway MAP
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| Up-regulation | Activity | CASP3 | Molecule Info |
Pathway MAP
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| Up-regulation | Activity | CASP9 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | CCND1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | COX-2 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | MMP-9 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | MYC | Molecule Info |
Pathway MAP
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| Down-regulation | Activity | p105 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | VEGFA | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | XIAP | Molecule Info |
Pathway MAP
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| In-vitro Model | PANC-1 | CVCL_0480 | Pancreatic ductal adenocarcinoma | Homo sapiens | ||
| BxPC-3 | CVCL_0186 | Pancreatic ductal adenocarcinoma | Homo sapiens | |||
| AsPC-1 | CVCL_0152 | Pancreatic ductal adenocarcinoma | Homo sapiens | |||
| In-vivo Model | Tumors were established by subcutaneous injection of 5*106 BxPC-3 cells into the flanks of male nude BALB/c mice. | |||||
| Experimental
Result(s) |
Shikonin can suppress the growth of human pancreatic tumors and potentiate the antitumor effects of gemcitabine through the suppression of NF-kappaB and NF-kappaB-regulated gene products. | |||||
| Dimethylaminoparthenolide | Lung cancer | Click to Show/Hide the Molecular Data of This Drug | ||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Representative Experiment Reporting the Effect of This Combination | [11] | |||||
| Detail(s) |
Combination Info
click to show the detail info of this combination
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| Biological
Regulation |
Alteration | Cellular metabolism | ||||
| In-vitro Model | Kasumi-2 | CVCL_0590 | B acute lymphoblastic leukemia | Homo sapiens | ||
| KOPN-8 | CVCL_1866 | B acute lymphoblastic leukemia | Homo sapiens | |||
| NALM-6 | CVCL_0092 | Adult B acute lymphoblastic leukemia | Homo sapiens | |||
| RCH-ACV | CVCL_1851 | B acute lymphoblastic leukemia | Homo sapiens | |||
| Reh | CVCL_1650 | B acute lymphoblastic leukemia | Homo sapiens | |||
| Experimental
Result(s) |
Combination of dimethylaminoparthenolide and shikonin alters metabolism and inhibits proliferation of pediatric precursor-B cell acute lymphoblastic leukemia. | |||||
| Target and Pathway | ||||
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| Target(s) | COVID-19 papain-like proteinase (PL-PRO) | Molecule Info | [1] | |
