Chlorogenic acid-inhibits Bcr-Abl tyrosine kinase and triggers p38 mitogen-activated protein kinase-dependent apoptosis in chronic myelogenous leukemic cells

被引:86
作者
Bandyopadhyay, G
Biswas, T
Roy, KC
Mandal, S
Mandal, C
Pal, BC
Bhattacharya, S
Rakshit, S
Bhattacharya, DK
Chaudhuri, U
Konar, A
Bandyopadhyay, S
机构
[1] Indian Inst Chem Biol, Div Immunol, Kolkata 700032, W Bengal, India
[2] Vivekananda Inst Med Sci, Kolkata, India
[3] Coll Med, Inst Haematol & Transfus Med, Kolkata, India
关键词
D O I
10.1182/blood-2003-11-4065
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 CMIL 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 p210(BCR-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. (C) 2004 by The American Society of Hematology.
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页码:2514 / 2522
页数:9
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