Synergistic inhibition of HTLV-1-infected cell proliferation by combination of cepharanthine and a tetramethylnaphthalene derivative.

The tetrahydrotetramethylnaphthalene derivative TMNAA has recently been identified as a selective inhibitor of human T-lymphotropic virus type 1 (HTLV-1)-infected T-cell lines and adult T-cell leukemia (ATL) cells but not of uninfected T-cell lines and peripheral blood mononuclear cells (PBMCs). Although the target molecule of TMNAA is still unknown, it does not inhibit nuclear factor-κB (NF-κB) activity. Therefore, TMNAA was examined for its inhibitory effect on the cell proliferation in combination with the NF-κB inhibitor cepharanthine. Synergism was observed for the combination, in inhibiting the proliferation of HTLV-1-infected T-cell lines. Although TMNAA alone did not induce the apoptosis of HTLV-1-infected T-cell lines, it strongly enhanced their apoptosis induced by cepharanthine. Thus, TMNAA may have potential as a therapeutic agent against ATL either alone or in combination with cepharanthine, which is clinically used as an anti-inflammatory drug in Japan.