Table 1.
Mechanism and function of esculetin in treatment of cancer.
| Pharmacological Mechanism | Inhibition/Activation/ Downregulation/Upregulation |
Model Used | Dosage | Application | Reference |
|---|---|---|---|---|---|
| Cell-cycle arrest at G1-phase Activate ARE pathway and impede binding interactions between Nrf2 and KEAP-1 Attenuate NF-κB pathway |
Human PANC-1 cells | 100 µM | In vitro | [45] | |
| Inhibit cell proliferation Induce autophagy by forming autophagic-vesicles Downregulate cyclin D1, D3, DK4 and DK2 Induce cell-cycle arrest at G0/G1-phase Block MEK/ERK phosphorylation by inhibiting Raf/MEK/ERK signaling |
Human leukemia cells (HL-60 cells) | 20 µM | In vitro | [47] | |
| Downregulate JNK/ERK signaling | Human leukemia cells (U937 cells) | 30 µM | In vitro | [48] | |
| Downregulate Bcl-2 and NF-κB expressions Induce apoptosis |
Benzo[a]pyrene-induced lung carcinogenesis in Swiss-albino mice | 50 mg/kg | In vivo | [50] | |
| Anti-cancer | Activate MAPK signaling Activate caspase-3 and 9 and cause apoptosis Release cytochrome c into cytosol Increase mitochondrial membrane depolarization Increase Bax expression |
Human colon cancer cells (HT-29 cells) | 55 µg/mL | In vitro | [51] |
| Suppress SP1, p27, cyclin D1, Mcl-1, survivin expressions Induce apoptosis |
Oral squamous cancer (HN22 and HSC4 cells) | 20 µg/mL | In vitro | [52] | |
| Downregulate STAT3 phosphorylation Inhibition of JAK/STAT pathways Induce cell-cycle arrest at G1/S-phase |
Laryngeal cancer (Hep2 cells) | 2, 10 µM | In vitro, In vivo | [53] | |
| Cell-cycle arrest at S-phase Elevate caspase-3, 9 expressions Reduce mitochondrial membrane potential Increase Bax expression Downregulate Bcl-2 expression |
Hepatocellular carcinoma (C57BL/6 mice were implanted with Hepa1–6 cells and SMMC-7721 cells) | 2.24 mM | In vitro, In vivo | [54] | |
| Suppress IGF-1/PI3K/Akt and IGF-1/MAPK signaling Reduce mitochondrial membrane potential Release cytochrome c from mitochondria Increase Bax, Bcl-2, caspase-3, 9 Expressions |
Human gastric cancer (MGC-803 and GES-1 cells) | 850 µM | In vitro | [55] | |
| Inhibit proliferation, migration and invasion of renal cancerous cells Induce cell-cycle arrest at G0/G1 and G2-phase Downregulate cyclin D1, CDK4, CDK6 and c-Myc expressions Increase E-cadherin level by decreasing N-cadherin and vimentin expressions |
Renal carcinoma (786-O and SN12-PM6 cells) | 200 µg/mL | In vitro | [56] |