Involvement of ROS in Chlorogenic Acid-Induced Apoptosis of Bcr-Abl+ CML Cells
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Involvement of ROS in Chlorogenic Acid-Induced Apoptosis of Bcr-Abl+ CML Cells
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| Creator |
Rakshit, Srabanti
Mandal, Labanya Pal, Bikas C Bagchi, Jayashree Biswas, Nabendu Chaudhuri, Jaydeep Chowdhury, Avik Acharya Manna, Anirban Chaudhuri, Utpal Konar, Aditya Mukherjee, Tulika Jaisankar , P Bandyopadhyay, Santu |
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| Subject |
Infectious Diseases and Immunology
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| Description |
Chlorogenic acid (Chl) has been reported to possess a wide range of biological and pharmacological
properties including induction of apoptosis of Bcr-Abl+ chronic myeloid leukemia (CML) cell lines and
clinical leukemia samples via inhibition of Bcr-Abl phosphorylation. Here we studied the mechanisms of
action of Chl in greater detail. Chl treatment induced an early accumulation of intracellular reactive
oxygen species (ROS) in Bcr-Abl+ cells leading to downregulation of Bcr-Abl phosphorylation and
apoptosis. Chl treatment upregulated death receptor DR5 and induced loss of mitochondrial membrane
potential accompanied by release of cytochrome c from the mitochondria to the cytosol. Pharmacological
inhibition of caspase-8 partially inhibited apoptosis, whereas caspase-9 and pan-caspase inhibitor
almost completely blocked the killing. Knocking down DR5 using siRNA completely attenuated Chlinduced
caspase-8 cleavage but partially inhibited apoptosis. Antioxidant NAC attenuated Chl-induced
oxidative stress-mediated inhibition of Bcr-Abl phosphorylation, DR5 upregulation, caspase activation
and CML cell death. Our data suggested the involvement of parallel death pathways that converged in
mitochondria. The role of ROS in Chl-induced death was confirmed with primary leukemia cells fromCML
patients in vitro as well as in vivo in nude mice bearing K562 xenografts. Collectively, our results establish
the role of ROS for Chl-mediated preferential killing of Bcr-Abl+ cells.
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| Date |
2010
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/1013/1/5_BP_2010.pdf
Rakshit, Srabanti and Mandal, Labanya and Pal, Bikas C and Bagchi, Jayashree and Biswas, Nabendu and Chaudhuri, Jaydeep and Chowdhury, Avik Acharya and Manna, Anirban and Chaudhuri, Utpal and Konar, Aditya and Mukherjee, Tulika and Jaisankar , P and Bandyopadhyay, Santu (2010) Involvement of ROS in Chlorogenic Acid-Induced Apoptosis of Bcr-Abl+ CML Cells. Biochemical Pharmacology, 80 (11). pp. 1662-1675. |
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| Relation |
http://dx.doi.org/10.1016/j.bcp.2010.08.013
http://www.eprints.iicb.res.in/1013/ |
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