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Blood, 15 August 2008, Vol. 112, No. 4, pp. 1424-1433. Prepublished online as a Blood First Edition Paper on June 9, 2008; DOI 10.1182/blood-2008-01-133769. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2008-01-133769v1 112/4/1424    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Buglio, D. Articles by Younes, A. Search for Related Content PubMed PubMed Citation Articles by Buglio, D. Articles by Younes, A. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Vorinostat inhibits STAT6-mediated TH2 cytokine and TARC production and induces cell death in Hodgkin lymphoma cell lines Daniela Buglio1, Georgios V. Georgakis1, Shino Hanabuchi2, Kazuhiko Arima2, Noor M. Khaskhely1, Yong-Jun Liu2, and Anas Younes1 Departments of1 Lymphoma/Myeloma and 2 Immunology, The University of Texas M. D. Anderson Cancer Center, Houston Epigenetic changes have been implicated in silencing several B-cell genes in Hodgkin and Reed-Sternberg cells (HRS) of Hodgkin lymphoma (HL), and this mechanism has been proposed to promote HRS survival and escape from immunosurveillance. However, the molecular and functional consequences of histone deacetylase (HDAC) inhibition in HL have not been previously described. In this study, we report that the HDAC inhibitor vorinostat induced p21 expression and decreased Bcl-xL levels causing cell-cycle arrest and apoptosis. Furthermore, vorinostat inhibited STAT6 phosphorylation and decreased its mRNA levels in a dose- and time-dependent manner, which was associated with a decrease in the expression and secretion of Thymus and Activation-Regulated Chemokine (TARC/CCL17) and interleukin (IL)–5 and an increase in IP-10 levels. Moreover, vorino-stat inhibited TARC secretion by dendritic cells that were activated by the thymic stromal lymphopoietin (TSLP). Collectively, these data suggest that pharmacologic HDAC inhibition in HL may induce favorable antitumor activity by a direct antiproliferative effect on HRS cells, and possibly by an immune mediated effect by altering cytokine and chemokines secretion in the microenvironment. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Pang, J. Kothapally, H. Mao, E. Tolbert, M. Ponnusamy, Y. E. Chin, and S. Zhuang Inhibition of histone deacetylase activity attenuates renal fibroblast activation and interstitial fibrosis in obstructive nephropathy Am J Physiol Renal Physiol, October 1, 2009; 297(4): F996 - F1005. [Abstract] [Full Text] [PDF] H. M. Prince, M. J. Bishton, and S. J. Harrison Clinical Studies of Histone Deacetylase Inhibitors Clin. Cancer Res., June 15, 2009; 15(12): 3958 - 3969. [Abstract] [Full Text] [PDF]

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