scholarly journals Antitumor Effect of Periplocin in TRAIL-Resistant Human Hepatocellular Carcinoma Cells through Downregulation of IAPs

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Chieh-Fang Cheng ◽  
I-Huang Lu ◽  
Hsiang-Wen Tseng ◽  
Chung-Yuan Sun ◽  
Li-Tsen Lin ◽  
...  

Cortex periplocae is the dried root bark ofPeriploca sepiumBge., a traditional Chinese herb medicine. It contains high amounts of cardiac glycosides. Several cardiac glycosides have been reported to inhibit tumor growth or induce tumor cell apoptosis. We extracted and purified cortex periplocae and identified periplocin as the active ingredient that inhibited the growth of TNF-related apoptosis-inducing ligand-(TRAIL-) resistant hepatocellular carcinoma cells. The antitumor activity of periplocin was further increased by TRAIL cotreatment. Periplocin sensitized TRAIL-resistant HCC through the following two mechanisms. First, periplocin induced the expression of DR4 and FADD. Second, the cotreatment of TRAIL and periplocin suppressed several inhibitors of apoptosis (IAPs). Both mechanisms resulted in the activation of caspase 3, 8, and 9 and led to cell apoptosis. In addition, intraperitoneal injection (IP) of periplocin repressed the growth of hepatocellular carcinoma (HCC) in xenograft tumor model in mice. In summary, periplocin sensitized TRAIL-resistant HCC cells to TRAIL treatment and resulted in tumor cell apoptosis and the repression of tumor growthin vivo.

2016 ◽  
Vol 130 (3) ◽  
pp. 614-625 ◽  
Author(s):  
Akinobu Ota ◽  
Haruhisa Nakao ◽  
Yumi Sawada ◽  
Sivasundaram Karnan ◽  
Md Wahiduzzaman ◽  
...  

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Chengshuo Zhang ◽  
Jialin Zhang ◽  
Xin Li ◽  
Ning Sun ◽  
Rui Yu ◽  
...  

Huaier aqueous extract, the main active constituent of Huaier proteoglycan, has antihepatocarcinoma activity in experimental and clinical settings. However, the potential and associated antihepatoma mechanisms of Huaier extract are not yet fully understood. Therefore, in this study, we aimed to elucidate the inhibitory proliferation effect of Huaier extract on apoptosis and cycle of HepG2 and Bel-7402 cells. Our data demonstrated that incubation with Huaier extract resulted in a marked decrease in cell viability dose-dependently. Flow cytometric analysis showed that a 48 h treatment of Huaier extract caused cell apoptosis. Typical apoptotic nucleus alterations were observed with fluorescence microscope after Hoechst staining. Immunoblot analysis further demonstrated that Huaier extract activated caspase 3 and PARP. Additionally, Huaier extract inhibited the activity of p-ERK, p-p38, and p-JNK in terms of MAPK. Furthermore, Huaier extract induced HCC cells arrest in S phase and decreased the cycle related protein expression ofβ-catenin and cyclin D1. Studies with JNK specific inhibitor, SP600125, showed that Huaier extract induced S phase arrest and decreasedβ-catenin and cyclin D1 expression via JNK signaling pathway. In conclusion, we verify that Huaier extract causes cell apoptosis and induces hepatocellular carcinoma cells arrest in S phase via JNK pathway, which advances our understanding on the molecular mechanisms of Huaier extract in hepatocarcinoma management.


2009 ◽  
Vol 18 (11) ◽  
pp. 1595-1604 ◽  
Author(s):  
Zheng Wang ◽  
Jian Zhou ◽  
Jia Fan ◽  
Shuang-Jian Qiu ◽  
Yao Yu ◽  
...  

2006 ◽  
Vol 66 (24) ◽  
pp. 11851-11858 ◽  
Author(s):  
Li Liu ◽  
Yichen Cao ◽  
Charles Chen ◽  
Xiaomei Zhang ◽  
Angela McNabola ◽  
...  

2012 ◽  
Vol 82 (2) ◽  
pp. 189-198 ◽  
Author(s):  
Rong Deng ◽  
Fen Yang ◽  
Shao-hua Chang ◽  
Jun Tang ◽  
Juan Qin ◽  
...  

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