       Document 0511
 DOCN  M9650511
 TI    Cell cycle inhibition of HTLV-I transformed T cell lines by retinoic
       acid: the possible therapeutic use of thioredoxin reductase inhibitors.
 DT    9605
 AU    U-Taniguchi Y; Furuke K; Masutani H; Nakamura H; Yodoi J; Institute for
       Virus Research, Kyoto University, Japan.
 SO    Oncol Res. 1995;7(3-4):183-9. Unique Identifier : AIDSLINE MED/96170919
 AB    Adult T cell leukemia derived factor (ADF), which was first reported as
       a cytokine-like factor produced by human T lymphotropic virus I
       (HTLV-I)-transformed T cells, is a human homologue of thioredoxin (TRX).
       ADF/TRX has multiple functions including growth promoting, antiapoptotic
       and radical scavenging activities, and is also involved in a wide
       variety of intracellular processes as a dithiol reducing agent in
       cooperation with the NADPH-TRX reductase system. In HTLV-1(+) T cell
       lines, HuT 102 and MT-2, which are ADF/TRX high producing cells, we
       found that the expression of ADF/TRX was dependent on the cell cycle and
       peaked at S phase. The reducing activity of ADF/TRX in these cells was
       also dependent on the cell cycle and elevated in S phase as determined
       by NADPH-dependent insulin degradation assay. Furthermore, inhibitors of
       TRX reductase, 13-cis-retinoic acid (13-cis-RA) and azelaic acid,
       inhibited the DNA synthesis of these cells. In contrast, the residual
       expression and reducing activity of ADF/TRX in HTLV-I(-) T cell lines
       did not show any significant correlation with the cell cycle. There was
       no distinct inhibitory effect of 13-cis-RA or azelaic acid on the growth
       of these ADF/TRX low producing cells. These results indicate that a high
       level of reducing activity of the ADF/TRX system may be required for the
       cell division of these virally transformed cells. This suggests that the
       TRX reductase inhibitors including retinoid derivatives have a potential
       therapeutic utility for treatment of HTLV-1(+) T cell leukemia without
       any effect on HTLV-I(-) cells.
 DE    Cell Cycle/DRUG EFFECTS  Cell Division/DRUG EFFECTS  Cell Line,
       Transformed  *Cell Transformation, Viral  Comparative Study
       Cytokines/METABOLISM  Dicarboxylic Acids/PHARMACOLOGY  Enzyme
       Inhibitors/*PHARMACOLOGY/THERAPEUTIC USE  Growth Substances/METABOLISM
       Human  HTLV-I/*PHYSIOLOGY  Insulin/METABOLISM  Neoplasm
       Proteins/METABOLISM  Support, Non-U.S. Gov't
       T-Lymphocytes/CYTOLOGY/DRUG EFFECTS/*VIROLOGY  Thioredoxin/METABOLISM
       Thioredoxin Reductase (NADPH)/*ANTAGONISTS & INHIB/METABOLISM
       Tretinoin/*PHARMACOLOGY  Tumor Cells, Cultured  Vitamin K/PHARMACOLOGY
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

