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Evidence-Based Complementary and Alternative Medicine
Volume 2015, Article ID 171356, 11 pages
Research Article

Huaier Aqueous Extract Induces Hepatocellular Carcinoma Cells Arrest in S Phase via JNK Signaling Pathway

1Department of Hepatobiliary Surgery and Unit of Organ Transplantation, First Hospital of China Medical University, 155 Nanjingbei Street, Heping District, Shenyang 110001, China
2Department of General Surgery, Fourth Hospital of China Medical University, 4 Chongshandong Road, Huanggu District, Shenyang 110032, China
3Department of Gastrointestinal Surgery, First Hospital of China Medical University, 155 Nanjingbei Street, Heping District, Shenyang 110001, China

Received 21 August 2014; Revised 12 November 2014; Accepted 12 November 2014

Academic Editor: Qing He

Copyright © 2015 Chengshuo Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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 of β-catenin and cyclin D1. Studies with JNK specific inhibitor, SP600125, showed that Huaier extract induced S phase arrest and decreased β-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.