title: Huaier Aqueous Extract Induces Hepatocellular Carcinoma Cells Arrest in S Phase via JNK Signaling Pathway.
abstract: 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.
authors.affiliation: Department of Hepatobiliary Surgery and Unit of Organ Transplantation, First Hospital of China Medical University, 155 Nanjingbei Street, Heping District, Shenyang 110001, China.
authors.forename: Chengshuo
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery and Unit of Organ Transplantation, First Hospital of China Medical University, 155 Nanjingbei Street, Heping District, Shenyang 110001, China.
authors.forename: Jialin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Fourth Hospital of China Medical University, 4 Chongshandong Road, Huanggu District, Shenyang 110032, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary Surgery and Unit of Organ Transplantation, First Hospital of China Medical University, 155 Nanjingbei Street, Heping District, Shenyang 110001, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Sun
authors.affiliation: Department of Hepatobiliary Surgery and Unit of Organ Transplantation, First Hospital of China Medical University, 155 Nanjingbei Street, Heping District, Shenyang 110001, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yu
authors.affiliation: Department of Hepatobiliary Surgery and Unit of Organ Transplantation, First Hospital of China Medical University, 155 Nanjingbei Street, Heping District, Shenyang 110001, China.
authors.forename: Bochao
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Department of Gastrointestinal Surgery, First Hospital of China Medical University, 155 Nanjingbei Street, Heping District, Shenyang 110001, China.
authors.forename: Dongyang
authors.initials: D
authors.lastname: Yu
authors.affiliation: Department of Hepatobiliary Surgery and Unit of Organ Transplantation, First Hospital of China Medical University, 155 Nanjingbei Street, Heping District, Shenyang 110001, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Hepatobiliary Surgery and Unit of Organ Transplantation, First Hospital of China Medical University, 155 Nanjingbei Street, Heping District, Shenyang 110001, China.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Liu