Trifolin acetate-induced cell death in human leukemia cells is dependent on caspase-6 and activates the MAPK pathway.

Authors:
Fernando Torres
Fernando Torres
University of Texas Southwestern Medical Center
United States
Jose Quintana
Jose Quintana
Hospital Galdakao-Usansolo (Osakidetza)-Red de Investigación en Servicios de Salud en Enfermedades Crónicas
Spain
Armando J Carmona
Armando J Carmona
Instituto Universitario de Bio-Orgánica Antonio González
Spain
Francisco Estevez
Francisco Estevez
Juan Canalejo Hospital
Spain

Apoptosis 2008 May;13(5):716-28

Department of Biochemistry, Instituto Canario de Investigación del Cáncer (I.C.I.C.), University of Las Palmas de Gran Canaria, Plaza Dr. Pasteur s/n, 35016, Las Palmas de Gran Canaria, Spain.

In the present study we demonstrated that the flavonoid derivative trifolin acetate (TA), obtained by acetylation of naturally occurring trifolin, induces apoptosis. Associated downstream signaling events were also investigated. TA-induced cell death was prevented by the non-specific caspase inhibitor z-VAD-fmk and reduced by the presence of the selective caspase inhibitors z-LEHD-fmk (caspase-9), z-DEVD-fmk (caspase-3) and z-VEID-fmk (caspase-6). The apoptotic effect of TA was associated with (i) the release of cytochrome c from mitochondria which was not accompanied by dissipation of the mitochondrial membrane potential (DeltaPsi(m)), (ii) the activation of the mitogen-activated protein kinases (MAPKs) pathway and (iii) abrogated by the over-expression of Bcl-2 or Bcl-x(L). TA-induced cell death was attenuated by inhibition of extracellular signal-regulated kinases (ERK) 1/2 with U0126 and inhibition of p38(MAPK) with SB203580. In contrast, inhibition of c-Jun NH(2)-terminal kinase (JNK) by SP600125 significantly enhanced apoptosis. Although reactive oxygen species (ROS) increased in response to TA, this did not seem to play a pivotal role in the apoptotic process since different anti-oxidants were unable to provide cell protection. The present study demonstrates that TA-induced cell death is mediated by an intrinsic-dependent apoptotic event involving mitochondria and MAPK, and through a mechanism independent of ROS generation.

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10495-008-0202-0DOI Listing

Still can't find the full text of the article?

We can help you send a request to the authors directly.
May 2008
4 Reads
5 Citations
3.685 Impact Factor

Publication Analysis

Top Keywords

cell death
16
ta-induced cell
12
cell
5
pivotal role
4
dissipation mitochondrial
4
accompanied dissipation
4
cytochrome mitochondria
4
mitochondria accompanied
4
mitochondrial membrane
4
role apoptotic
4
membrane potential
4
activation mitogen-activated
4
mitogen-activated protein
4
protein kinases
4
response play
4
deltapsim activation
4
release cytochrome
4
potential deltapsim
4
play pivotal
4
apoptotic associated
4

References

(Supplied by CrossRef)
Article in Cell Death Differ
G Kroemer et al.
Cell Death Differ 2005
Article in Science
NA Thornberry et al.
Science 1998
Article in Curr Opin Cell Biol
KM Boatright et al.
Curr Opin Cell Biol 2003
Article in Cell
S Nagata et al.
Cell 1997
Article in Science
RM Kluck et al.
Science 1997
Article in Science
J Yang et al.
Science 1997
Article in Cancer Res
F Essmann et al.
Cancer Res 2004
Article in Exp Cell Res
TG Cross et al.
Exp Cell Res 2000
Article in Leuk Res
C-D Kang et al.
Leuk Res 2000
Article in Pharmacol Rev
E Middleton et al.
Pharmacol Rev 2000
Article in Pharmacol Therapeut
BH Havsteen et al.
Pharmacol Therapeut 2002

Similar Publications