Abstract
Davidone C is a newly discovered flavonoid compound purified from the ethyl acetate-soluble fraction of Sophora davidii (Franch.) Skeels. This study explored the anti-tumor activity of davidone C on hepatocellular carcinoma HepG2 and Bel-7402 cells and its mechanism through MTT method, morphological observation, flow cytometry and Western blotting. The results showed that davidone C significantly inhibited the proliferation of HepG2 and Bel-7402 cells in a time- and dose-dependent manner. The morphological changes of apoptotic cells can be observed under an inverted microscope, such as cell floating, chromosome condensation, apoptotic bodies, and other phenomena. The expressions of Bax, cleaved caspase-9, cleaved caspase-3 and cleaved PARP increased with the increase of dosage while Bcl-2 decreased, suggesting that the apoptotic mechanism might be related to the mitochondrial apoptotic pathway. Moreover, davidone C administration can down-regulate the expression of Grp78, and simultaneously up-regulate the expression of caspase-7 and caspase-12, indicating that the apoptotic mechanism might be related to the ERS pathway. In addition, davidone C can down-regulate the expression of p62, and simultaneously up-regulate the expression of LC3-I and LC3-II with a quantitative dependence, suggesting that the mechanism of apoptosis may be related to the autophagy signal pathway. All these results showed davidone C has potential effects on hepatocellular carcinoma.
Highlights
Hepatocellular carcinoma was the most common primary liver cancer in clinical practice in the world [1], and it is an important medical problem
Hepatocellular carcinoma has been the main cause of death in patients with liver cirrhosis, and its incidence is expected to increase in the future
The purity of davidone C was more than 95% based on the high performance liquid chromatography (HPLC) analysis
Summary
Hepatocellular carcinoma was the most common primary liver cancer in clinical practice in the world [1], and it is an important medical problem. The morbidity and mortality of liver cancer are at the forefront of cancer types, and its survival rate is very low (18%). Liver cancer is listed as the sixth most common tumor and the third leading cause of death from cancer [3]. Hepatocellular carcinoma has been the main cause of death in patients with liver cirrhosis, and its incidence is expected to increase in the future. In order to further improve the survival rate of patients with hepatocellular carcinoma and improve treatment methods, it has become a top priority to find and discover new anti-cancer drugs
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