Targeting NF-kappaB and induction of apoptosis by novel NF-kappaB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) in Burkitt lymphoma cells.
A new NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), inhibited proliferation and induced apoptosis in human Burkitt lymphoma, HS-Sultan and Daudi cell lines. The activation of caspase-3 and the cleavage of caspase substrate PARP were observed after treatment with DHMEQ. The induction of apoptosis by DHMEQ was prevented by the pretreatment of Burkitt lymphoma cells with pan-caspase inhibitor, z-VAD-FMK. The expression of anti-apoptotic factors such as IAP-1 and XIAP was suppressed by DHMEQ. Phosphorylation of ERK and JNK was induced by DHMEQ. In conclusion, these results demonstrate that NF-kappaB might be an ideal target to develop for new anti-cancer drugs for Burkitt lymphoma.
Kimura
Noriko
N
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Miyakawa
Yoshitaka
Y
Kohmura
Kanoko
K
Umezawa
Kazuo
K
Ikeda
Yasuo
Y
Kizaki
Masahiro
M
D017209:Apoptosis; D001549:Benzamides / Q000494:pharmacology*; D002051:Burkitt Lymphoma / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003512:Cyclohexanones / Q000494:pharmacology*; D004789:Enzyme Activation; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation
D001549:Benzamides; D003512:Cyclohexanones; D016328:NF-kappa B; C464444:dehydroxymethylepoxyquinomicin; D053148:Caspase 3