title: Growth-suppressive effect of suberoylanilide hydroxamic acid (SAHA) on human oral cancer cells.
abstract: OBJECTIVE
  The histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) has been reported to exhibit anticancer activities in various cancer cell types, but as yet there are few reports on the anticancer effects of SAHA in oral squamous cell carcinoma (OSCC)-derived cells and xenograft models.
  
  
  METHODS
  The anti-proliferative and apoptotic activities of SAHA were assessed in human HSC-3 and HSC-4 (OSCC)-derived cell lines and JB6 normal mouse skin-derived epidermal cells using histone acetylation, soft agar colony formation, trypan blue exclusion, 4'-6-diamidino-2-phenylindole (DAPI) staining, Live/Dead viability/cytotoxicity and Western blot analyses.
  
  
  RESULTS
  We found that SAHA treatment resulted in hyperacetylation of histones H2A and H3 and a concomitant decrease in the viability of HSC-3 and HSC-4 cells. SAHA also significantly inhibited the neoplastic transformation of JB6 cells treated with TPA, whereas the viability of these cells was not affected by this treatment. Additionally, we found that SAHA suppressed the anchorage-independent growth (colony forming capacity in soft agar) of HSC-3 and HSC-4 cells. DAPI staining, Live/Dead and Western blot analyses revealed that SAHA can induce caspase-dependent apoptosis in HSC-3 and HSC-4 cells. We also found that SAHA treatment led to inhibition of ERK phosphorylation, and that two MEK inhibitors potentiated SAHA-mediated apoptosis. Okadaic acid treatment inhibited SAHA-mediated apoptosis in both the HSC-3 and HSC-4 cell lines, wheras SAHA induced a profound in vivo inhibition of tumor growth in HSC-3 xenografts.
  
  
  CONCLUSIONS
  Our results indicate that the ERK signaling pathway may constitute a critical denominator of SAHA-induced apoptosis in OSCC-derived cells and that SAHA may have therapeutic potential for OSCC.
authors.affiliation: Department of Oral Pathology, School of Dentistry, Institute of Oral Bioscience and Biodegradable Material, Chonbuk National University, Jeonju, 561-756, Republic of Korea.
authors.forename: Boonsil
authors.initials: B
authors.lastname: Jang
authors.affiliation: Department of Oral Pathology, School of Dentistry, Institute of Oral Bioscience and Biodegradable Material, Chonbuk National University, Jeonju, 561-756, Republic of Korea.
authors.forename: Ji-Ae
authors.initials: JA
authors.lastname: Shin
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Chonbuk National University, Jeonju, 561-756, Republic of Korea.
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Center of Animal Care and Use, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, 406-840, Republic of Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Oral Biochemistry, School of Dentistry, Institute of Oral Bioscience, Chonbuk National University, Jeonju, 561-756, Republic of Korea.
authors.forename: Ho-Keun
authors.initials: HK
authors.lastname: Yi
authors.affiliation: Division of Advanced Materials Engineering, Research Center for Advanced Materials Development and Institute of Biodegradable Materials, Chonbuk National University, Jeonju, 561-756, Republic of Korea.
authors.forename: Il-Song
authors.initials: IS
authors.lastname: Park
authors.affiliation: Department of Oral Pathology, School of Dentistry, Institute of Oral Bioscience and Biodegradable Material, Chonbuk National University, Jeonju, 561-756, Republic of Korea. efiwdsc@chonbuk.ac.kr.
authors.forename: Nam-Pyo
authors.initials: NP
authors.lastname: Cho
authors.affiliation: Department of Oral Pathology, School of Dentistry, Institute of Oral Bioscience and Biodegradable Material, Chonbuk National University, Jeonju, 561-756, Republic of Korea. npcho@chonbuk.ac.kr.
authors.forename: Sung-Dae
authors.initials: SD
authors.lastname: Cho
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009062:Mouth Neoplasms / Q000201:enzymology / Q000473:pathology*; D019319:Okadaic Acid / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D014410:Tumor Stem Cell Assay; D000077337:Vorinostat; D023041:Xenograft Model Antitumor Assays
chemical_list: D006657:Histones; D006877:Hydroxamic Acids; D047428:Protein Kinase Inhibitors; D019319:Okadaic Acid; D000077337:Vorinostat; D048049:Extracellular Signal-Regulated MAP Kinases; D020169:Caspases
keywords: Apoptosis; ERK; Oral cancer; Saha