Icariin, a natural flavonol glycoside, induces apoptosis in human hepatoma SMMC-7721 cells via a ROS/JNK-dependent mitochondrial pathway

Songgang Li; Ping Dong; Jianwei Wang; Jie Zhang; Jun Gu; Xiangsong Wu; Wenguang Wu; Xiaozhou Fei; Zhiping Zhang; Yong Wang; Zhiwei Quan; Yingbin Liu

doi:10.1016/j.canlet.2010.07.009

Icariin, a natural flavonol glycoside, induces apoptosis in human hepatoma SMMC-7721 cells via a ROS/JNK-dependent mitochondrial pathway

Cancer Lett. 2010 Dec 8;298(2):222-30. doi: 10.1016/j.canlet.2010.07.009. Epub 2010 Jul 31.

Authors

Songgang Li¹, Ping Dong, Jianwei Wang, Jie Zhang, Jun Gu, Xiangsong Wu, Wenguang Wu, Xiaozhou Fei, Zhiping Zhang, Yong Wang, Zhiwei Quan, Yingbin Liu

Affiliation

¹ Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University, Shanghai, China.

PMID: 20674153
DOI: 10.1016/j.canlet.2010.07.009

Abstract

In this study, the anticancer effect of icariin, a natural flavonol glycoside, against human hepatoma SMMC-7721 cells and the underlying mechanisms were investigated. Icariin triggered the mitochondrial/caspase apoptotic pathway indicated by enhanced Bax-to-Bcl-2 ratio, loss of mitochondrial membrane potential, cytochrome c release, and caspase cascade. Moreover, icariin induced a sustained activation of the phosphorylation of c-Jun N-terminal kinase (JNK) but not p38 and ERK1/2, and SP600125 (an inhibitor of JNK) almost reversed icariin-induced apoptosis in SMMC-7721 cells. In addition, icariin provoked the generation of reactive oxygen species (ROS) in SMMC-7721 cells, while the antioxidant N-acetyl cysteine almost completely blocked icariin-induced JNK activation and apoptosis. Taken together, these findings suggest that icariin induces apoptosis through a ROS/JNK-dependent mitochondrial pathway.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects*
Blotting, Western
Carcinoma, Hepatocellular / metabolism
Carcinoma, Hepatocellular / pathology
Carcinoma, Hepatocellular / prevention & control*
Caspase 3 / metabolism
Cell Line
Cell Line, Tumor
Cell Survival / drug effects
Cells, Cultured
Dose-Response Relationship, Drug
Drugs, Chinese Herbal / pharmacology
Female
Flavonoids / pharmacology*
Hep G2 Cells
Hepatocytes / cytology
Hepatocytes / drug effects
Hepatocytes / metabolism
Humans
JNK Mitogen-Activated Protein Kinases / metabolism
Liver Neoplasms, Experimental / metabolism
Liver Neoplasms, Experimental / pathology
Liver Neoplasms, Experimental / prevention & control
Mice
Mice, Inbred BALB C
Mice, Nude
Mitochondria / metabolism
Reactive Oxygen Species / metabolism
Signal Transduction / drug effects*
Xenograft Model Antitumor Assays

Substances

Drugs, Chinese Herbal
Flavonoids
Reactive Oxygen Species
JNK Mitogen-Activated Protein Kinases
Caspase 3
icariin