PMID- 17344917
OWN - NLM
STAT- MEDLINE
DCOM- 20070604
LR  - 20131121
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 21
IP  - 5
DP  - 2007 May
TI  - Fludarabine induces apoptosis of human T-cell leukemia virus type 1-infected T 
      cells via inhibition of the nuclear factor-kappaB signal pathway.
PG  - 1044-9
AB  - Adult T-cell leukemia/lymphoma (ATL) is a highly aggressive disease in which the 
      human T-cell lymphotropic virus type I (HTLV-I) has been recognized as the 
      etiologic agent. Fludarabine is a purine analog that has demonstrated significant 
      activity in B-cell malignancies, including chronic lymphocytic leukemia and 
      indolent non-Hodgkin's lymphoma. This study explored the effects of fludarabine 
      on HTLV-1-infected T cells (MT-1, -2, -4 and HUT102). Fludarabine induced growth 
      arrest and apoptosis of these cells, as measured by 
      3-(4,5-dimethylithiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, cell cycle 
      analysis and annexin V staining. Moreover, exposure of HTLV-1-infected T cells to 
      fludarabine decreased the levels of X-inhibitor of apoptosis protein in 
      conjunction with inhibition of nuclear factor kappaB (NF-kappaB)/DNA-binding 
      activity, as measured by Western blot analysis and electrophoretic mobility shift 
      and reporter gene assays, respectively. Further studies found that fludarabine 
      accumulated NF-kappaB and inhibitory subunit of NF-kappaB in cytosole in 
      conjunction with downregulation of NF-kappaB in nucleus, suggesting that 
      fludarabine blocked nuclear translocation of NF-kappaB. Taken together, 
      fludarabine may be useful for treatment of individuals with ATL and other types 
      of cancer in which NF-kappaB plays a role.
FAU - Nishioka, C
AU  - Nishioka C
AD  - Department of Hematology and Respiratory Medicine, Kochi Medical School, Kochi 
      University, Nankoku, Kochi, Japan.
FAU - Ikezoe, T
AU  - Ikezoe T
FAU - Yang, J
AU  - Yang J
FAU - Koeffler, H P
AU  - Koeffler HP
FAU - Taguchi, H
AU  - Taguchi H
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070308
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Antineoplastic Agents)
RN  - 0 (NF-kappa B)
RN  - FA2DM6879K (Vidarabine)
RN  - P2K93U8740 (fludarabine)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Cell Cycle/drug effects
MH  - Cells, Cultured
MH  - Human T-lymphotropic virus 1/*drug effects
MH  - Humans
MH  - Lymphocyte Activation/drug effects
MH  - NF-kappa B/*antagonists & inhibitors/metabolism
MH  - Signal Transduction/*drug effects
MH  - T-Lymphocytes/*drug effects/*virology
MH  - Vidarabine/*analogs & derivatives/pharmacology
EDAT- 2007/03/09 09:00
MHDA- 2007/06/05 09:00
CRDT- 2007/03/09 09:00
PHST- 2007/03/09 09:00 [pubmed]
PHST- 2007/06/05 09:00 [medline]
PHST- 2007/03/09 09:00 [entrez]
AID - 2404622 [pii]
AID - 10.1038/sj.leu.2404622 [doi]
PST - ppublish
SO  - Leukemia. 2007 May;21(5):1044-9. doi: 10.1038/sj.leu.2404622. Epub 2007 Mar 8.