RT Journal Article
SR Electronic
T1 Tyrosine Kinase Inhibitors Suppress the Growth of Non-Hodgkin B Lymphomas
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 163
OP 171
DO 10.1124/jpet.102.036723
VO 303
IS 1
A1 Hannah Ben-Bassat
A1 Zipora Hartzstark
A1 Rubina Levitzki
A1 Benjamin Y. Klein
A1 Zipora Shlomai
A1 Aviv Gazit
A1 Alexander Levitzki
YR 2002
UL http://jpet.aspetjournals.org/content/303/1/163.abstract
AB Non-Hodgkin lymphomas usually become resistant to chemotherapy and relapse due to the their intense antiapoptotic robustness. Furthermore, the slow growth of these malignancies limits the effectiveness of drugs aimed mainly at the proliferative pathways. Because protein tyrosine kinases (PTKs) play a key role in both proliferative and antiapoptotic pathways we screened our library of PTK inhibitors for agents that induce growth arrest and apoptosis in non-Hodgkin B cell lymphoma cell lines. Herein, we describe the identification of a family of PTK inhibitors whose most potent member is AGL 2592. This agent induces growth arrest and massive apoptosis in a number of non-Hodgkin lymphoma cell lines. We also show that the lymphoma cell lines are much more sensitive to this class of agents compared with other malignant carcinoma cells. AGL 2592 induces a dose-dependent and time-dependent inhibition of tyrosine phosphorylation of numerous proteins, including Stat3, and an increase of Bcl-2 phosphorylation, both biochemical hallmarks of growth inhibition and apoptosis. The American Society for Pharmacology and Experimental Therapeutics