Abstract
The overall survival rate of patients with hepatocellular carcinoma (HCC) has remained unchanged over the last several decades. Therefore, novel drugs and therapies are required for HCC treatment. Isoliquiritigenin (ISL), a natural flavonoid predominantly isolated from the traditional Chinese medicine Glycyrrhizae Radix (Licorice), has a high anticancer potential and broad application value in various cancers. Here, we aimed to investigate the anticancer role of ISL in the HCC cell line Hep3B. Functional analysis revealed that ISL inhibited the proliferation of Hep3B cells by causing G1/S cell cycle arrest in vitro. Meanwhile, the inhibitory effect of ISL on proliferation was also observed in vivo. Further analysis revealed that ISL could suppress the migration and metastasis of Hep3B cells in vitro and in vivo. Mechanistic analysis revealed that ISL inhibited cyclin D1 and up-regulated the proteins P21, P27 that negatively regulate the cell cycle. Furthermore, ISL induced apoptosis while inhibiting cell cycle transition. In addition, phosphatidylinositol 3′-kinase/protein kinase B (PI3K/AKT) signal pathway was suppressed by ISL treatment, and the epithelial marker E-cadherin was up-regulated when the mesenchymal markers Vimentin and N-cadherin were down-regulated. In brief, our findings suggest that ISL could be a promising agent for preventing HCC tumorigenesis and metastasis.
Highlights
Hepatocellular carcinoma (HCC) is considered as one of the most aggressive cancers with a low postoperative survival rate and high recurrence rate, and the 5-year survival rate is less than 20% [1,2]
The results showed that ISL is obviously cytotoxic to Hep3B cells with 50% inhibitory concentrations (IC50) of 42.84 +− 2.01 μM, and this effect is concentration- and time-dependent (Figure 1B)
It was demonstrated that ISL suppressed the proliferation ability of the HCC cell line Hep3B in vitro, and this inhibitory effect is associated with the inhibition of G1/S transition of the cell cycle
Summary
Hepatocellular carcinoma (HCC) is considered as one of the most aggressive cancers with a low postoperative survival rate and high recurrence rate, and the 5-year survival rate is less than 20% [1,2]. ISL exerts various pharmacological actions such as anti-viral, anti-microbial, anti-inflammatory, anti-oxidative, and immunomodulatory effects [3,4,5,6]. It exhibits anti-tumorigenic activities by inhibiting proliferation and angiogenesis, inducing apoptosis, causing cell cycle arrest, or obstructing metastasis in various types of cancer [7,8]. A wide spectrum of tumors has been demonstrated to be sensitive to ISL, including breast tumors, human cervical
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