Table 3. Upstream regulators presumably affected by shikonin and its derivatives after 24 h in U937 cells.
| Shikonin | Isobutyrylshikonin | β,β-Dimethylacrylshikonin | Isovalerylshikonin | 2-Methylbutyrylshikonin | |||||
|---|---|---|---|---|---|---|---|---|---|
| Activated | Inhibited | Activated | Inhibited | Activated | Inhibited | Activated | Inhibited | Activated | Inhibited |
| TP53 | MYC | PDGF BB | MYC | PDGF BB | MYC | FOXO3 | MYC | PDGF BB | MYC |
| ATF4 | BRD4 | ATF4 | BRD4 | CEBPA | BRD4 | NANOG | BRD4 | TNF | BRD4 |
| ATF2 | MAX | FOXO3 | Mek | TREM1 | Hdac | SMAD4 | TCR | Mek | |
| CDKN2A | TRIB3 | ELANE | MGEA5 | FOXO3 | Mek | RUVBL1 | TGM2 | mir-146 | |
| FOXL2 | MNT | TREM1 | TREM1 | MGEA5 | PAF1 | EGF | miR-155–5p | ||
| CEBPB | Mek | CEBPB | TP53 | HIF1A | PF4 | TAB1 | |||
| PGR | CDKN2A | TGM2 | PPRC1 | TREM1 | MGEA5 | ||||
| IGF1 | FOXL2 | CDKN2A | CCL5 | ||||||
| PPRC1 | TP53 | CEBPB | KRAS | ||||||
| FOXO1 | TGM2 | FOXO1 | Fcer1 | ||||||
| ERK1/2 | GLI1 | TGFB1 | |||||||
| IGF1 | SELPLG | IKBKB | |||||||
| FOXO1 | NEDD9 | NFkB | |||||||
| NFkB | EP300 | IRF3 | |||||||
| EP300 | Jnk | CEBPB | |||||||
| SELPLG | Cg | Jnk | |||||||
| PPRC1 | SELPLG | ||||||||
| Jnk | IGF1 | ||||||||
| CXCL12 | CAMP | ||||||||
| NEDD9 | |||||||||
| NEDD9 | |||||||||
The most likely activated and inhibited upstream regulators for each compound were underlined