title: Trichostatin A-induced apoptosis is mediated by Kruppel-like factor 4 in ovarian and lung cancer.
abstract: BACKGROUND
  The istone deacetylase (HDAC) inhibitor trichostatin A (TSA) is known to mediate the regulation of gene expression and anti proliferation activity in cancer cells. Kruppel-like factor 4 (klf4) is a zinc finger- containing transcription factor of the SP/KLF family, that is expressed in a variety of tissues and regulates cell proliferation, differentiation, tumorigenesis, and apoptosis. It may either either function as a tumor suppressor or an oncogene depending on genetic context of tumors.
  
  
  OBJECTIVE
  In this study, we tested the possibility that TSA may increase klf4 expression and cancer cell growth inhibition and apoptosis in SKOV-3 and A549 cells.
  
  
  METHODS
  The cytotoxicity of TSA was determined using the MTT assay test, while klf4 gene expression was assessed by real time PCR and to ability of TSA to induce apoptosis using a Vybrant Apoptosis Assay kit.
  
  
  RESULTS
  Our results showed that TSA exerted dose and time dependent cytotoxicity effect on SKOV-3 and A549 cells. Moreover TSA up-regulated klf4 expression. Flow cytometric analysis demonstrated that apoptosis was increased after TSA treatment.
  
  
  CONCLUSIONS
  Taken together, this study showed that TSA increased klf4 expression in SKOV3 and A549 cell lines, consequently, klf4 may played a tumor-suppressor role by increasing both cell growth inhibition and apoptosis. This study sheds light on the details of molecular mechanisms of HDACI-induced cell cycle arrest and apoptosis.
authors.affiliation: Hematology and Oncology Research Center, Tabriz, Iran E-mail : zarghami@tbzmed.ac.ir.
authors.forename: Sadeghi
authors.initials: S
authors.lastname: Zohre
authors.forename: Nejati-Koshki
authors.initials: NK
authors.lastname: Kazem
authors.forename: Akbarzadeh
authors.initials: A
authors.lastname: Abolfazl
authors.forename: Rahmati-Yamchi
authors.initials: RY
authors.lastname: Mohammad
authors.forename: Movassaghpour
authors.initials: M
authors.lastname: Aliakbar
authors.forename: Alizadeh
authors.initials: A
authors.lastname: Effat
authors.forename: Davoudi
authors.initials: D
authors.lastname: Zahra
authors.forename: Dariushnejad
authors.initials: D
authors.lastname: Hassan
authors.forename: Zarghami
authors.initials: Z
authors.lastname: Nosratollah
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*; D008175:Lung Neoplasms / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C012589:trichostatin A