CD40L-mediated inhibition of NF-kappaB in CA46 Burkitt lymphoma cells promotes apoptosis.
CD40/CD40L interaction on high-grade aggressive lymphomas such as Burkitt lymphoma results in a decrease in proliferation, whereas a transient increase in proliferation and survival in vitro is seen with indolent lymphomas. In this study, cell growth inhibition on human Burkitt lymphoma cell lines CA46 and Raji were obtained with either srhCD40L or pyrrolidine dithiocarbamate (PDTC), a specific inhibitor of NF-kappaB, whereas converse effects on CD40 negative control. Moreover, S phase arrest was demonstrated on CA46 cells in the presence of srhCD40L, and also cell apoptosis following exposed to srhCD40L or PDTC. Furthermore, nuclear factor-kappaB (NF-kappaB) DNA binding activity of CA46 cell extracts was markedly suppressed with srhCD40L or PDTC by electrophoretic mobility shift assays (EMSAs). Thus, the growth inhibition and apoptosis-inducing activity of srhCD40L via CD40-CD40 ligand interaction on Burkitt lymphoma cells was confirmed, and these effects may be attributable to the suppression of NF-kappaB binding activity. Hence, srhCD40L may provide clinical benefits in the treatment of CD40 positive carcinomas including human Burkitt lymphoma.
Wang
Shaoyuan
S
Department of Hematology, Fujian Institute of Hematology, Union Hospital of Fujian Medical University, Fuzhou, China. zjsywang@pub5.fz.fj.cn
Wang
Shaoxiong
S
Yang
Ting
T
Zhu
Fangbing
F
Zhu
Jinfeng
J
Huang
Yuanmao
Y
Wu
Liming
L
Chen
Lulu
L
Xu
Zhenshu
Z
D017209:Apoptosis / Q000187:drug effects; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000473:pathology; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D008024:Ligands; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology; D016196:S Phase / Q000187:drug effects; D013859:Thiocarbamates / Q000494:pharmacology
D019013:CD40 Antigens; D008024:Ligands; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; D023201:CD40 Ligand; C020972:pyrrolidine dithiocarbamic acid