¹Department of Hematology, Kinki University School of Medicine, Osaka, Japan

Correspondence: Dr Y Maeda, Department of Hematology, Kinki University School of Medicine, 377-2, Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan. Fax: +81 72 368 3732; E-mail: ymaeda@med.kindai.ac.jp

Received 19 December 2004; Accepted 7 March 2005; Published online 21 April 2005.

Abstract

We previously reported that all-trans retinoic acid (ATRA) inhibits growth in human T-cell leukemia virus type 1 (HTLV-1)-positive T-cell lines and fresh cells from patients with adult T-cell leukemia. However, the mechanism of this inhibition is not clear. In the present study, we observed that NF-B transcriptional activity as well as cell growth decreased significantly in HTLV-1-positive T-cell lines in the presence of ATRA. Furthermore, we observed that ATRA reduced HTLV-1 proviral DNA, HTLV-1 genes (gag, tax, or pol mRNA) using the real-time quantitative polymerase chain reaction. SIL-2R was reduced by ATRA in both protein level (culture supernantant) and mRNA level in HTLV-1-positive T-cell lines. Interestingly, ATRA significantly inhibited RT activity similar to azidothimidine (AZT) in HTLV-1-positive T-cell lines. Moreover, AZT inhibited proviral DNA but not NF-B transcriptional activity, and sIL-2R on HTLV-1; however, ATRA inhibited of NF-B, proviral DNA and sIL-2R on HTLV-1. These results suggested that the decrease in sIL-2R induced by ATRA may be caused by the actions of a NF-B inhibitor acting on the NF-B/sIL-2R signal pathway. These results suggested that ATRA could have two roles, as a NF-B inhibitor and as an RT inhibitor.