title: Chemosensitivity enhancement toward arsenic trioxide by inhibition of histone deacetylase in NB4 cell line.
abstract: OBJECTIVE
  To investigate the cytotoxic effects of suberanilohydroxamic acid (vorinostat) in combination with arsenic trioxide (ATO) on the human NB4 cell line in vitro.
  
  
  METHODS
  The rates of cell proliferation following treatment with vorinostat with or without ATO were measured. Flow cytometry of Annexin-V/propidium iodide double-stained cells was used to measure apoptosis. Acridine Orange and ethidium bromide staining was used to observe morphological changes characteristic of apoptosis. Western blot analysis was used to measure protein levels.
  
  
  RESULTS
  Vorinostat and ATO, alone and in combination, inhibited the proliferation of NB4 cells in a time- and dose-dependent manner and the effect was additive. NB4 cells treated with vorinostat + ATO demonstrated greater levels of apoptosis compared with cells treated with either drug alone. Both vorinostat and ATO alone and in combination resulted in lower levels of promyelocytic leukaemia/retinoic acid receptor alpha fusion protein and increased levels of acetyl-histone H3 and acetyl-histone H4 proteins compared with controls. Vorinostat + ATO resulted in lower levels of Akt protein compared with either drug alone.
  
  
  CONCLUSIONS
  The combination of vorinostat and ATO inhibited cell proliferation, induced apoptosis, and enhanced the chemosensitivity of NB4 cells. The mechanism might be associated with increasing histone acetylation levels as well as downregulation of the Akt signalling pathway.
authors.affiliation: Fujian Provincial Key Laboratory on Haematology, Department of Haematology, Fujian Institute of Haematology, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China.
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Internal Medicine, Fujian Provincial Hospital, Fuzhou, Fujian Province, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Guan
authors.affiliation: Fujian Provincial Key Laboratory on Haematology, Department of Haematology, Fujian Institute of Haematology, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: Fujian Provincial Key Laboratory on Haematology, Department of Haematology, Fujian Institute of Haematology, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China.
authors.forename: Yuanzhong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Fujian Provincial Key Laboratory on Haematology, Department of Haematology, Fujian Institute of Haematology, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China nainli@aliyun.com.
authors.forename: Nainong
authors.initials: N
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D010087:Oxides / Q000494:pharmacology*; D000077337:Vorinostat
chemical_list: D001152:Arsenicals; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D010087:Oxides; D000077337:Vorinostat; D006655:Histone Deacetylases; D000077237:Arsenic Trioxide
keywords: Histone deacetylase inhibitors; arsenic trioxide; NB4 cell line; apoptosis; all-trans retinoic acid; vorinostat