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Trichostatin A-induced Apoptosis is Mediated by Krüppel-like Factor 4 in Ovarian and Lung Cancer

  • Zohre, Sadeghi (Hematology and Oncology Research Center) ;
  • Kazem, Nejati-Koshki (Department of Medical Biotechnology, Faculty of Advanced Medical Science, Tabriz University of Medical Sciences) ;
  • Abolfazl, Akbarzadeh (Department of Medical Nanotechnology, Faculty of Advanced Medical Science, Tabriz University of Medical Sciences) ;
  • Mohammad, Rahmati-Yamchi (Hematology and Oncology Research Center) ;
  • Aliakbar, Movassaghpour (Department of Hematology, Faculty of Medicine, Tabriz University of Medical Sciences) ;
  • Effat, Alizadeh (Department of Medical Biotechnology, Faculty of Advanced Medical Science, Tabriz University of Medical Sciences) ;
  • Zahra, Davoudi (Department of Medical Biotechnology, Faculty of Advanced Medical Science, Tabriz University of Medical Sciences) ;
  • Hassan, Dariushnejad (Department of Medical Biotechnology, Faculty of Advanced Medical Science, Tabriz University of Medical Sciences) ;
  • Nosratollah, Zarghami (Hematology and Oncology Research Center)
  • Published : 2014.08.30

Abstract

Background: The istone deacetylase (HDAC) inhibitor trichostatin A (TSA) is known to mediate the regulation of gene expression and antiproliferation activity in cancer cells. Kr$\ddot{u}$ppel-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. Aims: 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. Materials and Methods: The cytotoxicity of TSA was determined using the MTT assay test, while klf4 gene expression was assessed by real time PCR andto 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.

Keywords

Histone deacetylase inhibitor;Trichostatin A;klf4;apoptosis

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