Table 2.
Pharmacological studies on the mechanisms of action of licorice in gastric cancer.
| Active Components of Licorice | Experimental Model | Mechanism of Action | Signaling Pathways Involved |
Journal Citation |
|---|---|---|---|---|
| Licoricidin (LCD) | In vitro: Human gastric cancer cell line of MGC-803 In vivo: Male nude mice 5 weeks old, 20 ± 2 g four groups (n = 6) Administration: Dosage; 10 mg/kg of LCD, 20 mg/kg of LCD, 20 mg/kg of 5-FU Route; Subcutaneous |
Inhibited cellular proliferation, cellular migration, and invasion, induced apoptosis and cell cycle arrest at G0/G1 phase. Inhibited tumor growth. |
Isoprenyl carboxyl methyltransferase (ICMT)/RAS pathway | [40] |
| Glycyrrhizic acid (GA) | Human gastric cancer cell line of MGC-803, BGC-823, and SGC-7901. | Inhibited cellular proliferation, promoted cell cycle arrest at G1/S-phase by ↓ cyclin D1, D2, D3, E1, and E2. Induced apoptosis by ↑ levels of Bax, cleaved PARP, and procaspase-3, -8, -9. | PI3K/AKT pathway | [41] |
| 18β-glycyrrhetinic acid (GRA) | In vitro: Human gastric cancer cell line of MKN-1, and BGC-823 In vivo: Male transgenic mice 6-week-old, two groups (n = 40) Administration: Dosage; distilled water containing 0.05% GRA Route; Oral |
Inhibited cellular proliferation, induced cell cycle arrest, and apoptosis. Inhibited tumor growth |
miR-149-3p-Wnt-1 signaling | [50] |
| Liquiritin (LIQ) + Cisplatin (DDP) |
Human gastric cancer cell line of SGC7901/DDP In vivo: male BALB/c-nu mice 5-week-old, 15–18 g four groups (n = 10) Administration: Dosage; 15 mg/kg of LIQ, 3 mg/kg of DDP Route; Intraperitoneal injection |
LIQ relatively inhibited the proliferation and migration of DDP-resistant gastric cancer cells. DDP+LIQ promoted cell cycle arrest at G0/G1 by ↓ cyclin D1, cyclin A, and ↑ CDK4 and p53 and p21. DDP+LIQ induced apoptosis and autophagy. Inhibited tumor growth of xenograft mice. |
[60] | |
| Licoflavone A (LA) | In vitro: Human gastric cancer cell line of SGC-7901, MKN-45, MGC-803and VEGF-stimulated MKN-45 cells. In vivo: Male BALB/c-nude mice 4–6-week-old, 18 ± 2 g Administration: Dosage; 50 mg/kg of LA Route; Oral |
Suppressed cellular proliferation. Induced apoptosis and cell cycle arrest at G1 phase, Inhibited the migration, invasion, and EMT of VEGF-stimulated MKN-45 cells. Inhibited tumor growth. |
PI3K/AKT and MEK/ERK signaling pathways. | [63] |
| Isoliquiritigenin (ISL) | In vitro: Human gastric cancer cell line of MKN28 |
Inhibited cellular proliferation, migration, and invasion. Promoted apoptosis and autophagy |
PI3K/AKT/mTOR | [44] |
| 18β-glycyrrhetinic acid (18β-GA) | In vitro: Human gastric cancer cell line of SGC-7901 |
Inhibited cellular proliferation, migration, and invasion. ↓ ROS formation, and expression of MMP-2 and 9, PKC-α, ERK, and vimentin. |
ROS/PKC-α/ERK pathway | [64] |
| Quercetin (QC) | In vivo: Human gastric cancer cell line of EBV (+) SNU719, EBV (−) MKN74 Female NOD/SCID mice five weeks old, two groups (n = 15) Administration: Dosage; 30 mg/kg of QC Route; Oral |
Inhibited tumor growth of the xenograft mice. Suppressed EBV viral proteins expression; (EBNA-1 and LMP-2) Promoted p53-dependent apoptosis by increasing the expression of caspase-3, -9, and Parp. |
[42] | |
| Licochalcone A (LCA) + 5-fluorouracil (5-FU) |
In vitro: Human gastric cancer cell line of SGC7901 and MKN-45 |
LCA suppressed cellular proliferation, induced apoptosis, and cell cycle arrest at G2/M transition. LCA+5-FU enhanced the anticancer effects. |
[65] | |
| Liquiritin (LIQ) + TRAIL |
In vitro: Human gastric cancer cell line of AGS and SNU-216. In vivo: Male BALB/c-nu mice 5 weeks old,15–18 g Administration: Dosage; 20 mg/kg of LIQ, 100 mg/mouse of TRAIL Route; Intraperitoneal |
Suppressed cellular proliferation, and migration. Induced apoptosis both in vitro and in vivo, enhanced activation of ROS and JNK. Inhibited tumor growth in vivo. |
[62] | |
| Licochalcone A | In vitro: Human gastric cancer cell line of AGS, MKN-28, and MKN-45. |
Inhibited cellular proliferation. Promoted cell cycle arrest at the G2/M transition by ↓ levels of cyclin A, B, and MDM2 and ↑ Rb expression. Induced apoptosis by regulating PARP, caspase-3, Bcl-2 and Bax expressions. |
[43] | |
| Glycyrrhetinic acid (GA) 11-deoxy glycyrrhetinic acid (11-DOGA) |
In vitro: Human gastric cancer cell line of BGC823 and SGC7901. In vivo: Nude Mice Administration: Dosage; 0, 10, 20, and 30 mg/kg of GA, 0, 10, 20, and 30 mg/kg of 11-DOGA Route; Subcutaneous injection |
Suppressed cellular proliferation. Promoted cell cycle arrest in G2 Phase by ↑ p21 expression and ↓ cdc2 and cyclin B1. Induced apoptosis by ↓ Bid expression and activated PARP cleavage. Inhibited tumor growth in vivo. |
Bid-mediated mitochondrial pathway. | [66] |
| Licochalcone A | In vitro: Human gastric cancer cell line of BGC. In vivo: SPF KM mice, 6–8 weeks, 13–15 g, two groups (n = 10). Administration: Dosage; 200 and 400 μM of LA Route; Intratumoral injection |
Inhibited cell proliferation, and induced apoptosis. Inhibited tumor growth in vivo. |
PI3K/AKT and ROS-mediated MAPK signaling pathway | [67] |