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Blood, 15 October 2004, Vol. 104, No. 8, pp. 2514-2522. Prepublished online as a Blood First Edition Paper on June 29, 2004; DOI 10.1182/blood-2003-11-4065. This Article Full Text (PDF) All Versions of this Article: 2003-11-4065v1 104/8/2514    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bandyopadhyay, G. Articles by Bandyopadhyay, S. Search for Related Content PubMed PubMed Citation Articles by Bandyopadhyay, G. Articles by Bandyopadhyay, S. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 2, 2003 Accepted June 2, 2004 Chlorogenic acid inhibits Bcr-Abl tyrosine kinase and triggers p38 mitogen-activated protein kinase-dependent apoptosis in chronic myelogenous leukemic cells Gautam Bandyopadhyay, Tanusree Biswas, Keshab C Roy, Swapan Mandal, Chhabinath Mandal, Bikas C Pal, Samir Bhattacharya, Srabanti Rakshit, Dilip K Bhattacharya, Utpal Chaudhuri, Aditya Konar, and Santu Bandyopadhyay* Immunology, Indian Institute of Chemical Biology, KolKata, West Bengal, India Medicinal Chemistry, Indian Institute of Chemical Biology, KolKata, West Bengal, India Molecular Endocrinology, Indian Institute of Chemical Biology, KolKata, West Bengal, India Drug Design, Development & Molecular Modelling, Indian Institute of Chemical Biology, KolKata, West Bengal, India Vivekananda Institute of Medical Sciences, KolKata, West Bengal, India Institute of Haematology & Transfusion Medicine, KolKata, West Bengal, India * Corresponding author; email: santu2{at}iicb.res.in. We report that chlorogenic acid (Chl) induces apoptosis of Bcr-Abl-positive several 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 two fold higher efficiency in killing K562 cells compared to Chl. NaChl also induces growth inhibition of squamous cell carcinoma (HSC-2) and salivary 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 MAP kinase may play important role in the anti-CML activity of Chl. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J.-C. Currie, S. Fortier, A. Sina, J. Galipeau, J. Cao, and B. Annabi MT1-MMP Down-regulates the Glucose 6-Phosphate Transporter Expression in Marrow Stromal Cells: A MOLECULAR LINK BETWEEN PRO-MMP-2 ACTIVATION, CHEMOTAXIS, AND CELL SURVIVAL J. Biol. Chem., March 16, 2007; 282(11): 8142 - 8149. [Abstract] [Full Text] [PDF]

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