Open AccessActivation of reactive oxygen species‐mediated mitogen‐activated protein kinases pathway regulates both extrinsic and intrinsic apoptosis induced by arctigenin in Hep G2
Author(s) -
Lu Zheng,
Zhou Hongbo,
Zhang Shishuo,
Dai Wei,
Zhang Yan,
Hong Liping,
Chen Fanjie,
Cao Jiyue
Publication year - 2020
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1111/jphp.13180
Subject(s) - apoptosis , p38 mitogen activated protein kinases , microbiology and biotechnology , kinase , reactive oxygen species , intrinsic apoptosis , phosphorylation , cytochrome c , fas ligand , mitogen activated protein kinase , signal transduction , biology , protein kinase a , chemistry , programmed cell death , caspase , biochemistry
Objectives Arctigenin (ARG) has been proved to inhibit the viability of hepatocellular carcinoma (HCC) via inducing apoptosis. However, the precise mechanism remains unknown. The present study was aimed to further investigate the mechanism of ARG against HCC in vitro and in vivo . Methods Arctigenin was applied in vitro and in vivo . Western blotting, immunohistochemistry, etc., were used to investigate the mechanisms. Key findings The time‐dependent enhancement of Bax/Bcl‐2 ratio, cytochrome c release, Fas and FasL levels, caspase cascade activation and the loss in the mitochondrial out membrane potential indicated that both intrinsic and extrinsic apoptotic pathways were triggered by ARG. Moreover, Jun NH2‐terminal kinase (JNK) and p38 phosphorylated time‐dependently. And inhibition of the phosphorylation of either p38 or JNK led to a significant reduction in HepG2 apoptosis, owing to the crucial roles of p38 and JNK played in regulating the apoptosis pathways. In addition, ARG increased the generation of reactive oxygen species (ROS) in HepG2 cells, while the antioxidant N‐acetyl cysteine almost reversed ARG‐induced JNK and p38 activation, and dramatically decreased cell apoptosis. In vivo , ARG increased the cell apoptosis in tumour tissues, and p‐p38, p‐JNK and Bax were significantly upregulated. Conclusions Our findings demonstrated that ARG induced apoptosis in HCC via ROS‐mediated mitogen‐activated protein kinases apoptosis pathway.