1. Isoliquiritigenin inhibits the proliferation, migration and metastasis of Hep3B cells via suppressing cyclin D1 and PI3K/AKT pathway
- Author
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Wu-Cha Zeng, Jian-Min Wu, Zhi-Wen Li, Xi Shi, Yun Huang, Rong-Jin Lin, Chen Liu, Guo-yan Xu, and Xuan-Yu Huang
- Subjects
0301 basic medicine ,cyclin D1 ,Apoptosis ,Vimentin ,Isoliquiritigenin ,Biochemistry ,Mice ,Phosphatidylinositol 3-Kinases ,chemistry.chemical_compound ,Chalcones ,0302 clinical medicine ,Cell Movement ,Research Articles ,Cancer ,Mice, Inbred BALB C ,biology ,Kinase ,Chemistry ,Cell Cycle ,Liver Neoplasms ,hepatocellular carcinoma ,Cell cycle ,030220 oncology & carcinogenesis ,Cell Cycle, Growth & Proliferation ,Cell Migration, Adhesion & Morphology ,Female ,Signal Transduction ,Carcinoma, Hepatocellular ,Biophysics ,Down-Regulation ,Mice, Nude ,03 medical and health sciences ,Cyclin D1 ,Cell Line, Tumor ,Animals ,Humans ,Molecular Biology ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,PI3K/AKT ,Cell Biology ,Gastrointestinal, Renal & Hepatic Systems ,digestive system diseases ,030104 developmental biology ,Cancer research ,biology.protein ,Proto-Oncogene Proteins c-akt - 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.
- Published
- 2020