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

Blood
Gautam BandyopadhyaySantu Bandyopadhyay

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 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 a...Continue Reading

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Citations

Jan 21, 2009·Apoptosis : an International Journal on Programmed Cell Death·Srabanti RakshitSantu Bandyopadhyay
Jan 19, 2012·Apoptosis : an International Journal on Programmed Cell Death·Nabendu BiswasSantu Bandyopadhyay
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Sep 21, 2013·Apoptosis : an International Journal on Programmed Cell Death·Jaydeep ChaudhuriSantu Bandyopadhyay
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Feb 9, 2011·Leukemia & Lymphoma·Amanda J RedigLeonidas C Platanias
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Sep 14, 2010·Biochemical Pharmacology·Srabanti RakshitSantu Bandyopadhyay
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