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.
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
Takeo
T
Ohsugi
Toshio
T
Kumasaka
Akira
A
Ishida
Takaomi
T
Ishida
Ryouichi
R
Horie
Toshiki
T
Watanabe
Kazuo
K
Umezawa
Kazunari
K
Yamaguchi
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