Perspectives on the Role of Isoliquiritigenin in Cancer

Abstract

Isoliquiritigenin (2',4',4-trihydroxychalcone, ISL), one of the most important bioactive compounds with a chalcone structure, is derived from licorice root. Licorice is commonly known as Glycyrrhiza, including Glycyrrhiza uralensis, Glycyrrhiza radix, and Glycyrrhiza glabra, which are generally available in common foods and Chinese herbal medicines based on a wide variety of biological functions and pharmacological effects, and its derivative (ISL) is utilized as a food additive and adjunct disease treatment. In this review, we summarized the progress over the last 10 years in the targeted pathways and molecular mechanisms of ISL that are involved in the regulation of the onset and progression of different types of cancers.

Keywords: apoptosis; cancer; cell signaling; isoliquiritigenin.

Figure 1

Metabolites of isoliquiritigenin (ISL). Phase I ISL metabolites were identified to be liquiritigenin (M1), 2′,4,4′,5′-tetrahydroxychalcone (M2), sulfuretin (M3), butein (M4), davidigenin (M5), and cis-6,4′-dihydroxyaurone (M6). Phase II metabolites were glucuronide conjugated process. Note: Figure was modified from [5,7,8].

Figure 2

Isoliquiritigenin (ISL) derivatives.

Figure 3

Molecular docking models. Interactions are represented in green (hydrogen bonding), orange (π–π stacking), purple (sigma-π) dash lines and gray (hydrophobic interaction: Van der Waals). (a) VEGFR-2; (b) EGFR; (c) GRP78; (d) SIRT1; (e) IKKβ; (f) DMNT1; (g) CK-2; (h) COX-2; (i) FLT3; (j) H2R; (k) TOPI.

Figure 4

Pharmacological effect of ISL. The scheme presents the biological effects of ISL and molecular mechanisms of ISL against cancer via various signal pathways.

Figure 5

ISL-mediated regulation of molecular targets underlying anti-tumor effects, including tumor proliferation suppression, apoptosis induction, EMT/metastasis, epigenetic responses and sensitization to chemotherapy. Downward arrows (↓) represent downregulation while upward arrows (↑) represent upregulation. This figure was modified from [55].

Figure 6

ISL exhibits significant anticancer activity through various mechanisms, such as proliferation suppression, apoptosis induction, and/or autophagy, and inhibits migration and invasion in various cancer cells.