Combination phototherapy with a histone deacetylase inhibitor and a potent DNA-binding bibenzimidazole: Effects in haematological cell lines

Current treatment for cutaneous T-cell lymphoma includes phototherapy, which involves either the use of narrowband ultraviolet B light or in combination with a psoralen photosensitiser. Therapy typically involves administration of the photosensitiser followed by topical exposure to . A different approach is extracorporeal photopheresis, an ex vivo strategy which is used for more advanced stages of disease. Further, histone deacetylase inhibitors are emerging as potent anticancer agents with suberoylanilide hydroxamic acid and depsipeptide, having received FDA approval for the treatment of cutaneous T-cell lymphoma. We have developed Sens, an extremely potent, DNA minor groove-binding sensitizer for potential use in phototherapy. We have previously demonstrated the extreme photopotency of Sens in human erythroleukemic K562 cells. Here we have extended those studies by investigating the photopotency of Sens in four haematological cell lines, namely, K562, T-cell leukaemic CEM-CCRF, P-glycoprotein overexpressing R100, and transformed B-lymphoblastoid cell lines (LCL) cells. In addition, we investigated the effects of suberoylanilide hydroxamic acid in combination with Sens. Using γH2AX as the endpoint, our findings indicate that Sens-induced phototoxicity in all four of the haematological cell lines. The addition of suberoylanilide hydroxamic acid augmented the photopotency of Sens highlighting the potential clinical applicability of combination therapies.