title: The effect of combined treatment with cisplatin and histone deacetylase inhibitors on HeLa cells.
abstract: OBJECTIVE
  To investigate the combined effects of cisplatin and the histone deacetylase (HDAC) inhibitors suberoylanilide hydroxamic acid (SAHA) or sirtinol on HeLa cells and assess the mechanism underlying HDAC inhibitor-cisplatin synergy.
  
  
  METHODS
  The antineoplastic actions of cisplatin, SAHA and sirtinol, alone and in combination, were evaluated using the tetrazolium dye-based MTT cell proliferation assay, DAPI nuclear staining and cytotoxicity analysis.
  
  
  RESULTS
  Exposure to cisplatin, SAHA or sirtinol alone induced a dose-dependent reduction in HeLa cell viability. Combined treatment with cisplatin and SAHA or sirtinol was significantly more cytotoxic than cisplatin alone. Individually, cisplatin, SAHA and sirtinol activated caspase-3 and induced apoptosis, but the effects of combined treatment were greater. Importantly, both HDAC inhibitors dose-dependently inhibited the expression of the antiapoptotic proteins Bcl-2 and x-linked inhibitor of apoptosis protein (XIAP).
  
  
  CONCLUSIONS
  The combination of cisplatin and SAHA or sirtinol had synergistic effect on the HeLa cell viability. This potentiation of cisplatin activity was associated with HDAC inhibitor-mediated down-regulation of Bcl-2 and XIAP. These may result from the relaxation of chromatin by these HDAC inhibitors that increase cisplatin sensitivity by enhancing the accessibility of DNA to cisplatin and transcriptional regulators.
authors.affiliation: Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Ke Long
authors.initials: KL
authors.lastname: Jin
authors.forename: Jeong-Yeol
authors.initials: JY
authors.lastname: Park
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Noh
authors.forename: Kwang Lae
authors.initials: KL
authors.lastname: Hoe
authors.forename: Joo Hak
authors.initials: JH
authors.lastname: Lee
authors.forename: Jong-Hyeok
authors.initials: JH
authors.lastname: Kim
authors.forename: Joo-Hyun
authors.initials: JH
authors.lastname: Nam