Bandyopadhyay, Gautam ; Biswas, Tanusree ; Roy, Keshab C. ; Mandal, Swapan ; Mandal, Chhabinath ; Pal, Bikas C. ; Bhattacharya, Samir ; Rakshit, Srabanti ; Bhattacharya, Dilip K. ; Chaudhuri, Utpal ; Konar, Aditya ; 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
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Official URL: http://bloodjournal.hematologylibrary.org/cgi/cont...
Related URL: http://dx.doi.org/10.1182/blood-2003-11-4065
Abstract
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) 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 mitogen-activated protein (MAP) kinase may play an important role in the anti-CML activity of Chl.
Item Type: | Article |
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Source: | Copyright of this article belongs to American Society of Hematology. |
ID Code: | 21532 |
Deposited On: | 22 Nov 2010 06:50 |
Last Modified: | 17 May 2016 05:44 |
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