%0 Journal Article
%T Combination Phototherapy with a Histone Deacetylase Inhibitor and a Potent DNA-Binding Bibenzimidazole: Effects in Haematological Cell Lines
%A Annabelle L. Rodd
%A Katherine Ververis
%A Tom C. Karagiannis
%J Lymphoma
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/405327
%X 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 ¦ÃH2AX 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. 1. Introduction Cutaneous T-cell lymphoma (CTCL) describes a heterogenous series of extranodal non-Hodgkin T-cell lymphomas that primarily appear in the skin [1, 2]. CTCL is characterised by an initial influx of T-cells of the CD4 phenotype in the skin, which have the propensity to home and accumulate in the blood and lymph nodes as the disease develops [2¨C4]. The two most common subtypes of CTCL include mycosis fungoides (MF), generally a low-grade lymphoma characterised by skin manifestations and the erythrodermic version S¨¦zary syndrome. S¨¦zary syndrome is an aggressive leukemic form of the disease identifiable by diffuse skin involvement (erythroderma), lymphadenopathy, and the presence of abnormal lymphoid cells circulating in the blood [5, 6]. Although a rare condition, with annual incidence of approximately 0.2¨C0.8 per 100,000 [7, 8], in its advanced or transformed stages, it is a debilitating disease, differing dramatically in its clinical and histopathologic presentations and subsequent therapeutic considerations [9]. While a plethora of treatments are available for CTCL, most remain palliative,
%U http://www.hindawi.com/journals/lymph/2012/405327/