Cell cycle inhibition of HTLV-I transformed T cell lines by retinoic acid: the possible therapeutic use of thioredoxin reductase inhibitors.

Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

Cell cycle inhibition of HTLV-I transformed T cell lines by retinoic acid: the possible therapeutic use of thioredoxin reductase inhibitors.

Oncol Res. 1995;7(3-4):183-9. Unique Identifier : AIDSLINE MED/96170919
U-Taniguchi Y; Furuke K; Masutani H; Nakamura H; Yodoi J; Institute for Virus Research, Kyoto University, Japan.

Abstract: 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.

Keywords: 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
960530
M9651056

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