The activation of p38 and JNK by ROS, contribute to OLO-2-mediated intrinsic apoptosis in human hepatocellular carcinoma cells

Zhenzhen Zhang, Chao Zhang, Ye Ding, Qian Zhao, Lifang Yang, Jingjing Ling, Ling Liu, Hui Ji, Yihua Zhang

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

In this study, we describe that a novel synthesized compound, olean-28,13β-olide 2 (OLO-2), exhibits selective cytotoxic activity via inducing apoptosis in human hepatocellular carcinoma (HCC) cell lines but not normal human hepatic cells in vitro. Exposure of human HCC HepG2 cells to OLO-2 results in significant loss of mitochondrial transmembrane potential (δ. Ψm), the release of cytochrome c, the recruitment of B-cell lymphoma 2 (Bcl-2) assaciated X protein (Bax) and the downregulation of Bcl-2. The apoptosis induced by OLO-2 is associated with the activation of caspase-3/9 and the nuclear translocation of apoptosis inducing factor (AIF). Moreover, the increase of phosphorylated p38 and c-Jun N-terminal kinase (JNK) is observed. OLO-2-induced the externalization of phosphatidyl-serine (PS) and the loss of δ. Ψm are blocked by p38 inhibitor SB203580 or JNK inhibitor SP600125. In addition, OLO-2 provokes the generation of reactive oxygen species (ROS) in HepG2 cells, while the antioxidant N-acetyl cysteine (NAC) almost completely blocks OLO-2-induced apoptosis and the activation of p38 and JNK. Taken together, the present study demonstrates that OLO-2 exhibits its cytotoxic activity through intrinsic apoptosis via ROS generation and the activation of p38 and JNK. Its potential to be a candidate of anti-cancer agent is worth being further investigated.

Original languageEnglish (US)
Pages (from-to)38-47
Number of pages10
JournalFood and Chemical Toxicology
Volume63
DOIs
StatePublished - Jan 2014

Keywords

  • Apoptosis
  • Cytotoxic
  • Human HCC cells
  • Mitochondria
  • OLO-2

ASJC Scopus subject areas

  • Food Science
  • Toxicology

Fingerprint Dive into the research topics of 'The activation of p38 and JNK by ROS, contribute to OLO-2-mediated intrinsic apoptosis in human hepatocellular carcinoma cells'. Together they form a unique fingerprint.

  • Cite this