Hydrogen peroxide/ATR-Chk2 activation mediates p53 protein stabilization and anti-cancer activity of cheliensisin A in human cancer cells
Metrics: PDF 2333 views | HTML 4206 views | ?
Jingjie Zhang1,*, Guangxun Gao1,2,*, Liang Chen1,*, Jingxia Li1, Xu Deng3, Qin-shi Zhao3 and Chuanshu Huang1
1 Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY, USA;
2 Department of Hematology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China;
3 State Key Laboratory of Phytochemistry and Plant Resources in West China,Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.
* These authors contributed equally to this work
Chuanshu Huang, email:
Qinshi Zhao, email:
Keywords: Cheliensisin A; Apoptosis; colon cancer; p53; chemotherapeutic agent
Received: January 21, 2014 Accepted: February 13, 2014 Published: February 14, 2014
Cheliensisine A (Chel A) as a novel styryl-lactone isolated from Goniothalamus cheliensis Hu has been indicated to be a chemotherapeutic agent in Leukemia HL-60 cells. However, its potential for cancer treatment and the underlying mechanisms are not deeply investigated to the best of our knowledge. Current studies showed that Chel A could trigger p53-mediated apoptosis, accompanied with dramatically inhibition of anchorage-independent growth of human colon cancer HCT116 cells. Further studies found that Chel A treatment resulted in p53 protein stabilization and accumulation via the induction of its phosphorylation at Ser20 and Ser15. Moreover, Chel A-induced p53 protein accumulation and activation required ATR/Chk2 axis, which is distinct from the mechanism that we have most recently identified the Chk1/p53-dependent apoptotic response by Chel A in normal mouse epidermal Cl41 cells. In addition, our results demonstrated that hydrogen peroxide generation induced by Chel A acted as a precursor for all these signaling events and downstream biological effects. Taken together, we have identified the Chel A as a new therapeutic agent, which highlights its potential for cancer therapeutic effect.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.