Journal of
Medicinal Plants Research

  • Abbreviation: J. Med. Plants Res.
  • Language: English
  • ISSN: 1996-0875
  • DOI: 10.5897/JMPR
  • Start Year: 2007
  • Published Articles: 3761

Full Length Research Paper

Hydroclathrus clathratus induces apoptosis in HL-60 leukaemia cells via caspase activation, upregulation of pro-apoptotic Bax/Bcl-2 ratio and ROS production

Kil-Nam Kim1,2, Min-Seok Yang1, Gi-Ok Kim1, Wook Jae Lee1,2, Nam Ho Lee2,3* and Chang-Gu Hyun1,2*
1Jeju Technopark,Jeju 690-121, Korea. 2Jeju Seaweed Industry Development Agency, Cheju National University, Jeju 690-756, Korea. 3Department of Chemistry, Cheju National University, Jeju 690-756, Korea.
Email: [email protected] or.kr/[email protected]

  •  Accepted: 02 August 2010
  •  Published: 09 March 2012

Abstract

Hydroclathrus clathratus is a well-known endemic alga in Korea having antiviral effects. In this study, its ability to induce cytotoxicity and apoptosis in cultured HL-60 human promyelocytic leukaemia cells was investigated. Treatment of the human promyelocytic leukaemia cell line (HL-60), cells with various concentrations of H. clathratus ethyl acetate extract (HCE) resulted in growth inhibition and induction of apoptosis in a dose-dependent manner, as determined by the cell viability, chromatin condensation, DNA fragmentation and sub-G1 phase accumulation. The HCE-induced apoptotic cell-death was associated with caspase-3 and caspase-9 activation, and poly ADP-ribose polymerase (PARP) degradation in the HL-60 cells. This increase in the HCE-induced apoptosis was also associated with a reduction in the levels of Bcl-xL, a potent cell-death inhibitor, and an increase in the levels of the Bax protein, which heterodimerises with and thereby inhibits Bcl-2. Finally, the intracellular reactive oxygen species (ROS), especially hydrogen peroxide (H2O2) and superoxide anion (O2), were found to be elevated after HCE treatment of these cells. In addition, antioxidant N-acetyl cysteine (NAC) pretreatment almost completely inhibited the HCE-induced apoptosis, suggesting that ROS are the key mediators of HCE-induced apoptosis. In conclusion, HCE induces apoptosis of human leukaemia cells through caspase activation, upregulation of the pro-apoptotic Bax/Bcl-2 ratio and ROS generation. Therefore, it may have anticancer properties valuable for application in food and drug products.

 

Key words: Apoptosis, Bcl-2, Hydroclathrus clathratus, reactive oxygen species.