Inhibitors of 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐induced multinucleated cell formation and HTLV‐I p19 antigen expression in HTLV‐I‐infected T‐cell line KH‐2Lo

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Abstract
To elucidate the biological mechanisms of 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐induced phenotypic changes in HTLV‐I virus‐infected human T‐cell line KH‐2Lo cells, inhibitors of TPA‐induced ornithine decarboxylase (ODC), protein kinases and calmodulin were examined for their effects on TPA‐induced multinucleated cell formation and HTLV‐I p19 antigen expression. Among the inhibitors of TPA‐induced ODC activity, α‐difluoromethyl ornithine (DFMO), I,25(OH)2D3 and its analogues, and retinoic acid were tested. As inhibitors of protein kinases, I‐(5‐isoquinolinyl‐sulfonyl)‐2‐methylpiperazine (H‐7), N‐[2‐(methylamino)ethyl]‐5‐isoquinoline‐sulfonamide (H‐8) and I,(5‐isoquinolynylsulfonyl)‐2,3‐dimethylpiperazine (H‐5) were used. In addition, a calmodulin inhibitor, N‐(4‐aminobutyl)‐5‐chlor‐2‐naphthalenesulfonamide (W13) and its inactive analogue, N‐(4‐aminobutyl)‐2‐naphthalenesulfonamide (W 12) were also tested. I,25(OH)2D3 and its active analogues inhibited both TPA‐induced HTLV‐I p19 antigen expression and multinucleated cell formation after 4 days of culture with TPA. On the other hand, an inhibitor of ODC, DFMO, the protein kinase inhibitors, the calmodulin inhibitor and retinoic acid suppressed TPA‐induced HTLV‐I p19 expression but did not suppress multinucleated cell formation.