Identification of protein kinase inhibitors with a selective negative effect on the viability of Epstein-Barr virus infected B cell lines.
Epstein-Barr virus (EBV) is a human herpesvirus, which is causally associated with the development of several B lymphocytic malignancies that include Burkitt's lymphomas, Hodgkin's disease, AIDS and posttransplant associated lymphomas. The transforming activity of EBV is orchestrated by several latent viral proteins that mimic and modulate cellular growth promoting and antiapoptotic signaling pathways, which involve among others the activity of protein kinases. In an effort to identify small molecule inhibitors of the growth of EBV-transformed B lymphocytes a library of 254 kinase inhibitors was screened. This effort identified two tyrosine kinase inhibitors and two MEK inhibitors that compromised preferentially the viability of EBV-infected human B lymphocytes. Our findings highlight the possible dependence of EBV-infected B lymphocytes on specific kinase-regulated pathways underlining the potential for the development of small molecule-based therapeutics that could target selectively EBV-associated human B lymphocyte malignancies.
School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Vassilis
V
Mavromatidis
Vichem Chemie Ltd., Budapest, Hungary.
Zoltan
Z
Varga
Vichem Chemie Ltd., Budapest, Hungary.
Frigyes
F
Waczek
Department of Molecular Biology, Max-Planck-Institute of Biochemistry, Martinsried, Germany.
Zoltán
Z
Őrfi
Vichem Chemie Ltd., Budapest, Hungary; Department of Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary.
László
L
Őrfi
Vichem Chemie Ltd., Budapest, Hungary; MTA-SE Pathobiochemistry Research Group, Department of Medical Chemistry, Semmelweis University, Budapest, Hungary.
György
G
Kéri
School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
George
G
Mosialos
D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000821:virology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D004854:Herpesvirus 4, Human / Q000472:pathogenicity*; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*
D047428:Protein Kinase Inhibitors