Record Details

ICB3E Induces INOS Expression by ROS-Dependent JNK and ERK Activation for Apoptosis of Leukemic Cells

EPrints@IICB

View Archive Info
 
 
Field Value
 
Title ICB3E Induces INOS Expression by ROS-Dependent JNK
and ERK Activation for Apoptosis of Leukemic Cells
 
Creator Biswas, Nabendu
Mahato, Sanjit Kumar
Acharya Chowdhury, Avik
haudhuri, Jaydeep C
Manna, Anirban
Vinayagam, Jayaraman
Chatterjee, Sourav
Jaisankar , P
Chaudhuri, Utpal
Bandyopadhyay, Santu
 
Subject Cancer Biology and Inflammatory Disorder Division
Chemistry
 
Description The role of c-Jun N terminal Kinase (JNK) has
been well documented in various cellular stresses where it
leads to cell death. Similarly, extracellular signal-regulated
kinase (ERK) which was identified as a signalling molecule
for survival pathway has been shown recently to be
involved in apoptosis also. Recently we reported that
ICB3E, a synthetic analogue of Piper betle leaf-derived
apoptosis-inducing agent hydroxychavicol (HCH), possesses
anti-chronic myeloid leukemia (CML) acitivity in
vitro and in vivo without insight on mechanism of action.
Here we report that ICB3E is three to four times more
potent than HCH in inducing apoptosis of leukemic cells
without having appreciable effects on normal human
peripheral blood mononuclear cells, mouse fibroblast cell
line NIH3T3 and monkey kidney epithelial cell line Vero.
ICB3E causes early accumulation of mitochondria-derived
reactive oxygen species (ROS) in K562 cells. Unlike HCH,
ICB3E treatment caused ROS dependent activation of both JNK, ERK and induced the expression of iNOS leading to
generation of nitric oxide (NO). This causes cleavage of
caspase 9, 3 and PARP leading to apoptosis. Lack of
cleavage of caspase 8 and inability of blocking chimera
antibody to DR5 or neutralizing antibody to Fas to reverse
ICB3E-mediated apoptosis suggest the involvement of only
intrinsic pathway. Our data reveal a novel ROS-dependent
JNK/ERK-mediated iNOS activation pathway which leads
to NO mediated cell death by ICB3E
 
Publisher Kluwer
 
Date 2012
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1481/1/APOPTOSIS___17(_6)__612%2D626;2012[6].pdf
Biswas, Nabendu and Mahato, Sanjit Kumar and Acharya Chowdhury, Avik and haudhuri, Jaydeep C and Manna, Anirban and Vinayagam, Jayaraman and Chatterjee, Sourav and Jaisankar , P and Chaudhuri, Utpal and Bandyopadhyay, Santu (2012) ICB3E Induces INOS Expression by ROS-Dependent JNK and ERK Activation for Apoptosis of Leukemic Cells. Apoptosis, 17 (6). pp. 612-626.
 
Relation http://dx.doi.org/10.1007/s10495-011-0695-9
http://www.eprints.iicb.res.in/1481/