Oncotarget

Research Papers:

Alisol B 23-acetate induces autophagic-dependent apoptosis in human colon cancer cells via ROS generation and JNK activation

Yueliang Zhao, Edmund T.S. Li and Mingfu Wang _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2017; 8:70239-70249. https://doi.org/10.18632/oncotarget.19605

Metrics: PDF 1510 views  |   HTML 2352 views  |   ?  


Abstract

Yueliang Zhao1, Edmund T.S. Li1 and Mingfu Wang1

1School of Biological Sciences, The University of Hong Kong, Hong Kong, China

Correspondence to:

Mingfu Wang, email: [email protected]

Keywords: alisol B 23-acetate, autophagy, apoptosis, ROS, JNK

Received: March 29, 2017     Accepted: June 16, 2017     Published: July 26, 2017

ABSTRACT

Alisol B 23-acetate (AB23A), a natural triterpenoid from the rhizome of Alisma orientale, a Chinese medicinal herb, has multiple physiological activities including anticancer. However, its effect on human colon cancer and the underlying mechanism are not clear. Here, we reported for the first time that AB23A induced cell cycle G1 phase arrest and apoptotic cell death in colon cancer cells. Autophagy also occurred in AB23A-treated HCT116 cells as evidenced by the accumulation of microtubule-associated protein 1 light chain 3 form II (LC3-II) and degradation of SQSTM1/p62. An autophagy inhibitor, 3-methyladenine (3-MA) was found to attenuate AB23A-mediated autophagy, apoptosis, and cell death, indicating that AB23A-induced apoptotic response was dependent on the induction of autophagy. In addition, the treatment of HCT116 cells with AB23A resulted in the generation of reactive oxygen species (ROS) and phosphorylation of c-Jun N-terminal kinase (JNK). A ROS scavenger, N-acetylcysteine (NAC) and a JNK-specific inhibitor, SP600125 attenuated AB23A-induced autophagy and apoptotic cell death. Moreover, NAC was able to eliminate AB23A-induced JNK phosphorylation. This finding provides a novel mechanism of action of AB23A in colon cancer HCT116 cells that AB23A induces autophagic-dependent apoptotic cell death in colon cancer cells, at least in part, though the accumulation of intracellular ROS and subsequent activation of JNK.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 19605