Inhibitory Effect of Hernandezine on the Proliferation of Hepatocellular Carcinoma

被引:1
作者
Kuok, Chiufai [1 ]
Wang, Qi [2 ]
Fong, Pedro [1 ]
Qin, Yong [2 ]
Meng, Lirong [1 ]
机构
[1] Macao Polytech Univ, Fac Hlth Sci & Sports, Macau 999078, Peoples R China
[2] China Pharmaceut Univ, Sch Tradit Chinese Med, Nanjing 210009, Peoples R China
关键词
hepatocellular carcinoma; apoptosis; phosphatidylinositol; 3-kinase; protein kinase B; reactive oxygen species; hernandezine; AMPK ACTIVATOR HERNANDEZINE; PI3K/AKT PATHWAY; CELLS; TETRANDRINE; CANCER; MEDICINE; RESISTANCE; SORAFENIB; MECHANISM; APOPTOSIS;
D O I
暂无
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Hepatocellular carcinoma (HCC) causes 830000 deaths every year and is becoming the third malignant tumor worldwide. One of the primary reasons is the lack of effective drugs. Hernandezine (HER), a bisben-zylisoquinoline alkaloid of Thalictrum simplex, has been confirmed to have antitumor activity. But there are few reports about its effect on HCC and the underlying mechanisms still remain unclear. Therefore, the antitumor effects and mechanisms of HER on HCC were evaluated in HepG2 and Hep3B cells. The in vitro experiments demonstrated that HER significantly induced G0/G1 phase arrest, inhibited the proliferation and promoted cell apoptosis in liver cancer cell lines. In the mechanisms, the antitumor effects of HER on liver cancer cells were mediated by phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) pathway and reactive oxygen species (ROS), simultaneously. In one way, HER inhibited the activities of PI3K-AKT pathway, which interrupt the dimer formation of cyclin-dependent kinase 4 (CDK4) and cyclin D1 (CCND1) and result to G0/G1 phase arrest. In another way, after HER treatment, ROS accumulated in liver cancer cells and caused mitochondria injury which further influenced the expression of apoptosis-related proteins and eventually resulted to HepG2 and Hep3B cell apoptosis. In addition, HER showed a tumor restrain func-tion in HepG2 and Hep3B bearing nude mice. Overall, these findings indicated that HER is a promising anti-tumor drug, which may provide a new direction for clinical HCC treatment.
引用
收藏
页码:245 / 256
页数:12
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