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We report that chlorogenic acid (Chl) induces apoptosis of several Bcr-Ablpositive chronic myelogenous leukemia (CML) cell lines and primary cells from CML patients in vitro and destroys BcrAbl-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 BcrAbl kinase leading to activation of p38 mitogen-activated protein ( IntroductionChronic myelogenous leukemia (CML) is a malignant clonal disorder of hematopoietic stem cells leading to massive expansion of myeloid lineage cells. 1 The natural fate of CML is to progress from a benign chronic phase into the fatal blast crisis between approximately 3 and 5 years. Development of CML is associated with a specific chromosomal translocation known as the Philadelphia (Ph) chromosome that is detectable throughout the course of the disease. 2 Somatic mutation in Ph chromosome originates from reciprocal translocation between the long arms of chromosomes 9 and 22 and fuses Bcr with c-Abl genetic sequences. Both the Bcr-Abl fusion proteins p210 and p185 can cause CML or acute leukemia. 3,4 The p210 form of Bcr-Abl is seen in 95% of CML and in 20% of acute lymphocytic leukemia, whereas the p185 form is identified in about 10% of acute lymphocytic leukemia patients. 5,6 The Bcr-Abl fusion proteins are constitutively active non-receptor tyrosine kinases whose activity is essential for transforming abilities. 7 An almost universal presence of Bcr-Abl in CML patients made this fusion protein an attractive target for drug development. Bcr-Abl inhibitors, STI571, adaphostin, and PD173955, are capable of inducing a variable degree of apoptosis in human CML cells. [8][9][10] The signal transduction pathways involved in mediating apoptosis by Bcr-Abl inhibitors are poorly defined. In the current study, we describe a novel Bcr-Abl kinase inhibitor that triggers p38 mitogen-activated protein (MAP) kinase-dependent apoptosis of Bcr-Abl-positive CML cells. Materials and methods Cells and reagentsThe Ph chromosome ϩ CML cell line K562, 11 Ph chromosome-negative T-...

Surface free energy (SFE) is a property resulted from the chemical structure and the orientation of the molecules at the surface boundary of the materials. For solids, it can be calculated from the contact angles of liquid drops with known surface tension, formed on the solid surface. There are various SFE evaluation methods based on different theoretical assumptions. In this study, SFE and the dispersive, polar, acidic and basic components of the SFE of a polymeric material, poly(methyl methacrylate) (PMMA), were calculated by using Zisman, Saito, Fowkes, Berthelot, Geometric mean, Harmonic mean, and Acid–base approaches. The results obtained from various liquid couples or triplets were compared. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008