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Chlorogenic Acid Inhibits Bcr-Abl Tyrosine Kinase and Triggers p38 mitogen-activated Protein Kinase–Dependent Apoptosis in Chronic Myelogenous Leukemic Cells

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Title Chlorogenic Acid Inhibits Bcr-Abl Tyrosine Kinase and Triggers p38
mitogen-activated Protein Kinase–Dependent Apoptosis in Chronic
Myelogenous Leukemic Cells
 
Creator Bandyopadhyay, Gautam
Biswas, Tanusree
Roy, Keshab C
Mandal, Swapan Kumar
Mandal, Chhabinath
Pal, Bikas C
Bhattacharya, Samir
Rakshit, Srabanti
Bhattacharya, Dilip K
Chaudhuri,, Utpal
Konar, Aditya
Bandyopadhyay, Santu
 
Subject Chemistry
Infectious Diseases and Immunology
 
Description We report that chlorogenic acid (Chl) induces apoptosis of several Bcr-Abl– positive chronic myelogenous leukemia (CML) cell lines and primary cells from
CML patients in vitro and destroys Bcr-Abl–positive K562 cells in vivo. In contrast, this compound has no effect on the growth and viability of Bcr-Abl–negative lymphocytic and myeloid cell lines and primary CML cells. Sodium chlorogenate (NaChl) exhibits 2-fold higher efficiency in killing K562 cells compared with Chl.NaChl also induces growth inhibition of squamous cell carcinoma (HSC-2) andsalivary gland tumor cells (HSG), although at 50-fold higher concentration. NaChl inhibits autophosphorylation of p210Bcr-Abl fusion
protein rapidly.We demonstrate that p38 phosphorylation is increased
in Bcr-Abl–positive cells after treatment with NaChl and closely paralleled the inhibition of Bcr-Abl phosphorylation. NaChl did not increase phosphorylation of p38 in Bcr-Abl–negative cells including HSC-2 and HSG that are responsive to this compound, indicating that p38 activation by NaChl is dependent on Bcr-Abl kinase inhibition. Inhibition of p38 activity by SB203580 significantly reduced NaChl-induced apoptosis of K562 cells, whereas activation of p38 by anisomycin
augmented the apoptosis. These findings indicate that inhibition of Bcr- Abl kinase leading to activation of p38 mitogen-activated protein (MAP) kinase may play an important role in the anti- CML activity of Chl.
 
Publisher American Society of Hematology
 
Date 2004
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1617/1/Blood%2C_2004.pdf
Bandyopadhyay, Gautam and Biswas, Tanusree and Roy, Keshab C and Mandal, Swapan Kumar and Mandal, Chhabinath and Pal, Bikas C and Bhattacharya, Samir and Rakshit, Srabanti and Bhattacharya, Dilip K and Chaudhuri,, Utpal and Konar, Aditya and Bandyopadhyay, Santu (2004) Chlorogenic Acid Inhibits Bcr-Abl Tyrosine Kinase and Triggers p38 mitogen-activated Protein Kinase–Dependent Apoptosis in Chronic Myelogenous Leukemic Cells. Blood, 104 (8). pp. 2514-2522. ISSN 0006-4971
 
Relation http://dx.doi.org/10.1182/blood-2003-11-4065
http://www.eprints.iicb.res.in/1617/