Table 4.
Anti-hepatocellular cancer effects of coumarins.
| Coumarin compound | Dose | Mechanisms | Model | Cell line | Ref |
|---|---|---|---|---|---|
| Hydroxypyridinone-coumarin | 2 µM | Induced autophagy, inhibited proliferation, activated ERK1/2, down-regulated the Akt pathway | In vitro | MHCC97 HepG |
(210) |
| Furanocoumarin | 100 μM | Anti cancer effect | In vitro | HepG2 | (134) |
| Coumarin-3-carboxylic acid | 0–1000 µM. | Inhibited DNA synthesis not by intercalation. Ames tests showed that all the tested agents or phase I metabolites were non-mutagenic | In vitro | CHANG Hep-G2 |
(211) |
| Esculetin | 2.24 mM | Triggered mitochondrial caspase-dependent apoptosis |
In vivo
In vitro |
Hepa1-6 | (212) |
| Osthole | 161.4 mM 137.0 mM | Inhibited HCC growth in vivo and in vitro, induced apoptosis by repressing NF-kB, increased expression of apoptosis-related genes. | In vivo | Hepa1-6 HepG2 |
(213) |
| 4-Hydroxy-3-nitro-coumarin Ligand silver + 4-oxy-3-nitro-coumarin-bis (phenanthroline) |
0, 20, 40, 80 μM for 4 h or 24 h IC50 at 4h = 80 µM and at 24 h =40 μM |
Inhibited proliferation | In vitro | HepG2 CHANG |
(214) |
| Coumarin-dioxy-acetic acid (cdoa) copper-coumarin-dioxyacetic acetate-phenathroline [Cu(cdoa)(phen)2] |
0, 7.5, 15, 30 µM | [Cu(cdoa)(phen)2] inhibited proliferation more than the parent ligand [CdoaH2], phen, or the simple salt. Biochemical and morphological features consistent with both necrotic and apoptotic cell death |
In vitro | Hep-G2 | (215) |
| Novel synthetic coumarins | 50 µM | Inhibited expression of NF-kB targeted genes | In vitro | HepG2 | (216) |
| Natural coumarin | 4.9 µM | Increased necrosis Inhibited tumor growth |
In vitro
In vivo |
HepG2 | (217) |
| Clausarin, dentatin, nordentatin, xantoxyletin | IC50 (µM) 17.6 ± 2.1 47.6 ± 2.8 29.9 ± 3.2 78.2 ± 2.2 |
Clausarin had the highest selective cytotoxicity. Xantoxyletin caused apoptosis and lowest necrosis in HepG2 cells after 24 h | In vitro | HepG2 | (218) |
| Coumarin-triazole hybrid | IC50 = 0.80 μM. | Inhibited proliferation | In vitro | HepG2 | (219) |
| Thiazolylpyrazolyl coumarin derivatives | IC50 = 5.4 – 10.7 µM | Anticancer activity | In vitro | HepG2 | (220) |
| Coumarin hybrids | IC50 = 0.49-3.96μM | Inhibited proliferation | In vitro | Hep G2 | (221) |
| 7,8-Dihydroxy-3-(4-nitrophenyl) coumarin | IC50 = 17.65 μM | Cell cycle arrest at S phase, loss of mitochondrial membrane potential, mediated ROS-independent cell death | In vitro | HepG2 | (177) |
| 7-Hydroxy-6,8-dimethoxy-2H-1-benzopyran-2-one (isofraxidin) | IC50 = 100 μM | Inhibited invasion without influencing proliferation or attachment. Inhibited TPA-induced matrix metalloproteinase-7 (MMP-7) at both protein and mRNA levels. More effective at low cell density than at high density. Inhibited phosphorylation of ERK1/2, without affecting NF-kB nuclear translocation, activator protein-1 (AP-1) DNA binding activity, or degradation of IkB. |
In vitro | HuH-7, HepG2 | (222) |
| Juglansoside C extracted from bark of Juglans mandshurica. | IC50 = 70.9 μM | Showed moderate cytotoxicity Induced apoptosis in Hep3B cells |
In vitro | Hep3B | (223) |
| 7-OH-4-Methylcoumarin | IC50 = 356 µM | Inhibited proliferation in a dose-dependent manner. Reversed malignant phenotype and caused re-differentiation. |
In vitro | SMMC-7721 | (224) |