A novel matrine derivative WM622 inhibits hepatocellular carcinoma by inhibiting PI3K/AKT signaling pathways

• Published in: Molecular and cellular biochemistry 2018-12, Vol.449 (1-2), p.47-54
• Main Authors: Sun, Xiao, Zhuo, Xiao-bin, Hu, Yi-ping, Zheng, Xuan, Zhao, Qing-jie
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Alkaloids - chemistry; Alkaloids - pharmacology; Animals; Apoptosis; Biochemistry; Biomedical and Life Sciences; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cardiology; Cell cycle; Cell Line, Tumor; Cell proliferation; Digestive system; Epidermal growth factor receptors; Fibrosis; G1 phase; G1 Phase Cell Cycle Checkpoints - drug effects; G1 Phase Cell Cycle Checkpoints - genetics; Hepatitis B; Hepatocellular carcinoma; Herbal medicine; Humans; Life Sciences; Liver; Liver cancer; Liver Neoplasms - drug therapy; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Male; Medical Biochemistry; Mice; Mice, Inbred BALB C; Mice, Nude; Oncology; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Proto-Oncogene Proteins c-akt - metabolism; Quinolizines - chemistry; Quinolizines - pharmacology; Resting Phase, Cell Cycle - drug effects; Resting Phase, Cell Cycle - genetics; Signal Transduction - drug effects; Signal Transduction - genetics; Signaling; Traditional Chinese medicine; Tumors
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-018-3341-9

Hepatocellular carcinoma (HCC) is among the most common lethal cancers of the digestive system with poor prognosis rates and ineffective therapeutic options. Matrine, a traditional Chinese medicine found in the roots of sophora species, has been used in the clinical treatment of liver fibrosis, chronic hepatitis B and other diseases. We have synthesized a matrine derivatives named WM622 (C26H35ON3S2) with a significant inhibitory effect on transplanted tumors in vivo. The half inhibitory concentration (IC50) of WM622 is 34 µM, which is much lower than matrine. WM622 inhibited the proliferation and promoted apoptosis of hepatocellular carcinoma cells significantly, and the cell cycle was blocked in G0/G1 phase. The protein phosphorylation levels of EGFR, AKT, PI3K and GSK3β (p-EGFR, p-AKT, p-PI3K, and p-GSK3β) were also decreased by WM622 treatment dose dependently. In tumor-bearing mice, WM622 could reduce the tumor volumes. In conclusion, the study demonstrated that WM622 could inhibit the proliferation of the hepatocellular carcinoma both in vivo and in vitro by inducing apoptosis, blocking cell cycle in G0/G1 phase and inhibiting the PI3K/AKT signal pathways.