title: Histone deacetylase inhibitors potentiate photochemotherapy in cutaneous T-cell lymphoma MyLa cells.
abstract: Cutaneous T cell lymphomas (CTCL) represent rare extranodal non-Hodgkin's lymphomas, which are characterised by pleomorphic skin lesions and distinct T-cell markers. CTCL is a relatively benign disease in its early stages, but survival rates decrease significantly with progression. Histone deacetylase inhibitors (HDACi) have recently emerged as a new class of targeted anticancer therapies for CTCL, which have been shown to induce growth inhibition, terminal differentiation and apoptosis in various cancers in vitro and in vivo. In addition to the intrinsic anticancer properties of HDACi, recent studies have demonstrated its ability to synergise with phototherapy. In particular, we examine the therapeutic potential of HDACi in combination with ultraviolet A (UV-A) phototherapy, employing a halogenated DNA minor groove binding ligand called UVASens as a photosensitiser. In vitro studies have demonstrated that UVASens is approximately 1000-fold more potent than current psoralens. The extreme photopotency of UVASens allows the use of lower radiation doses minimising the carcinogenic risks associated with the long-term use of phototherapy. Considering, previous findings using the photosensitiser UVASens and potential synergy of HDACi with phototherapy, it was hypothesised that HDACi will augment photochemotherapy-induced cytotoxicity in CTCL MyLa cells. The findings indicated that combinations of UVASens/UV-A photochemotherapy and HDACi significantly decreased cell viability and increased apoptosis and DNA double-strand breaks in MyLa cells.
authors: Epigenomic Medicine, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia; Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.
authors: Jane J
authors: JJ
authors: Sung
authors: Epigenomic Medicine, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia; Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.
authors: Katherine
authors: K
authors: Ververis
authors: Epigenomic Medicine, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia; Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia. Electronic address: tom.karagiannis@bakeridi.edu.au.
authors: Tom C
authors: TC
authors: Karagiannis
mesh_terms: D001549:Benzamides / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy* / Q000473:pathology; D010778:Photochemotherapy / Q000379:methods*; D011725:Pyridines / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D000077337:Vorinostat
chemical_list: D001549:Benzamides; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D011725:Pyridines; C118739:entinostat; D000077337:Vorinostat
keywords: Cutaneous T-cell lymphoma; DNA double-strand breaks; Histone deacetylase inhibitors; Histone deacetylases; Iodinated DNA ligand; Phototherapy