Adult T-cell leukemia/lymphoma (ATL/ATLL) is an aggressive lymphoid disease caused by human T-cell leukemia virus type 1 (HTLV-1). It is reported that retinoid suppressed the proliferation of malignant cells including ATL cells. In this study, we showed the mechanism of retinoid action for ATL cells. We observed that NF-kB transcriptional activity as well as cell proliferation decreased in HTLV-1-positive T-cell lines by treatment with retinoid. Further, we observed that retinoid reduced HTLV-1

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... proviral DNA. Interestingly, retinoid significantly inhibited reverse transcriptase (RT) activity similar to azidothimidine (AZT) on HTLV-1-positive T-cell lines. Therefore, AZT was inhibitory of proviral DNA load but not NF-kB transcriptional activity on HTLV-I, however retinoid was inhibitory of both NF-?B and proviral DNA on HTLV-1. Furthermore, we showed cellular senescence in HTLV-I positive T-cell lines and in primary ATL cells obtained from acute ATL patients. The number of senescent cells significantly increased in the HTLV-I positive T-cell lines after treatment with retinoid, but not in the HTLV-I negative ones. These results indicated that retinoid could have three roles, as a NF-?B inhibitor, as a RT inhibitor and as a facilitating cellular senescence.