Mechanisms underlying isoliquiritigenin‐induced apoptosis and cell cycle arrest via ROS‐mediated MAPK/STAT3/NF‐κB pathways in human hepatocellular carcinoma cells

Abstract

Isoliquiritigenin (ISL), a natural flavonoid isolated from plant licorice, has various pharmacological properties, including anticancer, anti‐inflammatory, and antiviral effects. However, the underlying mechanisms and signaling pathways of ISL in human hepatocellular carcinoma (HCC) cells remain unknown. In this study, we evaluated the effects of ISL on the apoptosis of human HCC cells with a focus on reactive oxygen species (ROS) production. Our results showed that ISL exhibited cytotoxic effects on two human liver cancer cells in a dose‐dependent manner. ISL significantly induced mitochondrial‐related apoptosis and cell cycle arrest at the G2/M phase, which was accompanied by ROS accumulation in HepG2 cells. However, pretreatment with an ROS scavenger, N‐acetyl‐l‐cysteine (NAC), inhibited ISL‐induced apoptosis. In addition, ISL increased the phosphorylation levels of c‐Jun N‐terminal kinase (JNK), p38 kinase and inhibitor of NF‐κB (IκB), and decreased the phosphorylation levels of extracellular signal‐regulated kinase (ERK), signal transducer and activator of transcription 3 (STAT3), nuclear factor‐kappa B (NF‐κB), these effects were blocked by NAC and mitogen‐activated protein kinase (MAPK) inhibitors. Taken together, the findings of this study indicate that ISL induced HepG2 cell apoptosis via ROS‐mediated MAPK, STAT3, and NF‐κB signaling pathways. Therefore, ISL may be a potential treatment for human HCC, as well as other cancer types.

Cytisine exerts anti-tumour effects on lung cancer cells by modulating reactive oxygen species-mediated signalling pathways

“…There is increasing evidence indicating that ROS mediates intracellular signal cascades and excessive ROS production leads to intracellular stress, mitochondria dysfunction, and disturbance of the balance of redox reactions, ultimately causing cell apoptosis or necrosis [26,27]. Association between lung cancer risk and oxidative stress has been well recognized.…”

Isoliquiritigenin Suppressed Esophageal Squamous Carcinoma Growth by Blocking EGFR Activation and Inducing Cell Cycle Arrest

“…In addition to the same pharmacological effect as licorice, ILQ also exerted antidiabetic and antispasmodic activities [15,16]. Recently, multiple studies had investigated the effect of ILQ on cancers, and ILQ has exhibited profound antitumor abilities against breast cancer, hepatocellular carcinoma, colon cancer, cervical cancer, prostate cancer, endometrial cancer, and so on [17][18][19][20][21][22]. So far, the direct target of ILQ in tumor cells has not been elaborated, but several nonspecific mechanisms modulated by ILQ have been reported.…”

Physiological and Biochemical Mechanisms Mediated by Allelochemical Isoliquiritigenin on the Growth of Lettuce Seedlings

“…This indicates that isoliquiritigenin effectively induces the overproduction of ROS in lettuce radicles. Other recent studies have highlighted the importance of ROS-mediated damage induced by isoliquiritigenin in A375 human melanoma cells and hepatocellular carcinoma cells [28,29]. Therefore, ROS could be a major factor causing isoliquiritigenin-induced allelopathic activity.…”