Combination Phototherapy with a Histone Deacetylase Inhibitor and a Potent DNA-Binding Bibenzimidazole : Effects in Haematological Cell Lines

Abstract EN

Current treatment for cutaneous T-cell lymphoma includes phototherapy, which involves either the use of narrowband ultraviolet B light or UVA in combination with a psoralen photosensitiser.

Therapy typically involves administration of the photosensitiser followed by topical exposure to UVA.

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 UVASens, an extremely potent, DNA minor groove-binding UVA sensitizer for potential use in phototherapy.

We have previously demonstrated the extreme photopotency of UVASens in human erythroleukemic K562 cells.

Here we have extended those studies by investigating the photopotency of UVASens 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 UVASens.

Using γH2AX as the endpoint, our findings indicate that UVASens-induced phototoxicity in all four of the haematological cell lines.

The addition of suberoylanilide hydroxamic acid augmented the photopotency of UVASens highlighting the potential clinical applicability of combination therapies.