In vitro and in vivo antitumor activity of the NF-kappaB inhibitor DHMEQ in the human T-cell leukemia virus type I-infected cell line, HUT-102.
Adult T-cell leukemia (ATL) is an aggressive neoplasm caused by human T-cell leukemia virus type I (HTLV-I). The NF-kappaB pathway is activated in ATL cells and in virus-infected cells, and plays a central role in oncogenesis. We examined the effect of the novel NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on a well-characterized HTLV-I-infected cell line, HUT-102, in vitro and in vivo. DHMEQ inhibited translocation of NF-kappaB p65 to the nucleus and induced apoptotic cell death in vitro. In vivo, DHMEQ inhibited the growth and infiltration of HUT-102 tumor cells transplanted subcutaneously in SCID mice lacking natural killer cell activity.
Ohsugi
Takeo
T
Division of Microbiology and Genetics, Center for Animal Resources and Development, Institute of Resource Development and Analysis, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan. ohsugi@gpo.kumamoto-u.ac.jp
Kumasaka
Toshio
T
Ishida
Akira
A
Ishida
Takaomi
T
Horie
Ryouichi
R
Watanabe
Toshiki
T
Umezawa
Kazuo
K
Yamaguchi
Kazunari
K
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D003512:Cyclohexanones / Q000008:administration & dosage / Q000494:pharmacology*; D015368:Human T-lymphotropic virus 1; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009368:Neoplasm Transplantation; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000378:metabolism
D001549:Benzamides; D003512:Cyclohexanones; D009363:Neoplasm Proteins; D051996:Transcription Factor RelA; C464444:dehydroxymethylepoxyquinomicin