Planta Med 2011; 77 - PM148
DOI: 10.1055/s-0031-1282906

Anticancer effect of a cembrenolide diterpene LS-1 in colon cancer cells through activation of oxidative stress

E Kim 1, J Hong 1, J Kang 1, D Park 2, Y Koh 3, E Yoo 1, H Kang 1
  • 1Department of Pharmacology, Jeju National University, Jeju, South Korea
  • 2Department of Histology, Jeju National University, Jeju, South Korea
  • 3Department of Microbiology, Jeju National University, Jeju, South Korea

We observed that (1S,2S,3E,7E,11E)-3,7,11,15-Cembratetraen-17,2-olide (LS-1), marine cembrenolide diterpene, inhibited growth and induced apoptosis in colon cancer cells via a ROS dependent mechanism. Treatment of HT-29 cells with LS-1 resulted in ROS generation, which was accompanied by disruption of mitochondrial membrane potential, cytosolic release of cytochrome c, sub-G1 peak accumulation, activation of Bid, caspase-3, -8, and -9, and cleavage of PARP along with the suppressive expression of Bcl-2. All these effects were significantly blocked on pretreatment with the ROS inhibitor N-acetylcystein (NAC), indicating the involvement of increased ROS in the proapoptotic activity of LS-1. Moreover, we showed that LS-1 induced the phosphorylation of JNK and dephosphorylation of p38, ERK, Akt, Src and STAT3, which were effectively attenuated by NAC. In addition, the expression of antioxidant catalase was abrogated by treatment using LS-1 with or without NAC. These findings reveal the novel anticancer efficacy of LS-1 mediated by the induction of apoptosis via ROS generation in human colon cancer cells.

Keywords: LS-1; cembrenolide diterpene; HT-29; Apoptosis; ROS

Acknowledgement: This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government (NRF-2009–351–2-E00072) and Jeju National University Hospital Research fund (2010).