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Iron chelation by chlorogenic acid as a natural antioxidant
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http://tinyurl.com/5unq2
Blood. 2004 Oct 15;104(8):2514-22. Epub 2004 Jun 29. Related Articles, Links
Chlorogenic acid inhibits Bcr-Abl tyrosine kinase and triggers p38
mitogen-activated protein kinase-dependent apoptosis in chronic myelogenous
leukemic cells.
Bandyopadhyay G, Biswas T, Roy KC, Mandal S, Mandal C, Pal BC, Bhattacharya S,
Rakshit S, Bhattacharya DK, Chaudhuri U, Konar A, Bandyopadhyay S.
Division of Immunology, Indian Institute of Chemical Biology, 4, Raja S. C.
Mullick Rd, Kolkata-, India.
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 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.
PMID: 15226183 [PubMed - in process]
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