Induction of Apoptosis by Methyl Alcohol Extract of Enteromorpha linza (Linnaeus) J Agardh in U937 Human Leukemia Cells

  • E-O Choi
  • H-S Kim
  • M-H Han
  • C Park
  • B-W Kim
  • JA Hwang
  • Y Choi
  • H-J Hwang
Keywords: Enteromorpha linza, Apoptosis, Caspase, U937 cells


Purpose: To investigate the anti-cancer effect of methyl alcohol extract of Enteromorpha linza (Linnaeus) J. Agardh (MEEL) in U937 human leukemia cells.
Methods: Cytotoxicity was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Apoptosis was detected using 4',6-diamidino-2-phenylindole (DAPI) staining, agarose gel electrophoresis, and flow cytometry. Protein levels were determined by Western blot analysis. Caspase activity was measured spectrophotometrically at 405 nm.
Results: MEEL inhibited U937 cell proliferation and induced apoptosis through up-regulation of death receptor-related gene expression, caspase-8 activation and truncation of Bid, which was associated with the loss of mitochondrial membrane potential. Subsequently, the levels of anti-apoptotic proteins such as Bcl-2 and Bcl-xL, and IAP family proteins decreased but those of pro-apoptotic proteins including Bax and Bad increased in MEEL-treated U937 cells. MEEL treatment also resulted in activation of caspase-9 and -3 as well as concomitant cleavage of poly(ADP-ribose) polymerase and phopholipase Cγ-1. However, pretreatment of U937 cells with z-VAD-fmk, a pan caspase inhibitor, abrogated chromatin condensation and DNA fragmentation and prevented cell death induced by the MEEL.
Conclusion: The findings suggest that MEEL induced apoptosis in U937 cells through a signaling cascade of death-receptor-mediated extrinsic as well as mitochondria-mediated intrinsic pathways, thus raising the possibility that MEEL may be of value in the development of novel therapeutic approaches for treating leukemia.

Keywords: Enteromorpha linza, Apoptosis, Caspase, U937 cells


Journal Identifiers

eISSN: 1596-9827
print ISSN: 1596-5996