ORBi: Crisanti Cecilia - The HDAC inhibitor panobinostat (LBH589) inhibits mesothelioma and lung cancer cells in vitro and in vivo with particular efficacy for small cell lung cancer

Reference : The HDAC inhibitor panobinostat (LBH589) inhibits mesothelioma and lung cancer cells in ...


	Document type :	Scientific journals : Article
	Discipline(s) :	Human health sciences : Oncology
	To cite this reference:	http://hdl.handle.net/2268/83490

Title :	The HDAC inhibitor panobinostat (LBH589) inhibits mesothelioma and lung cancer cells in vitro and in vivo with particular efficacy for small cell lung cancer
Language :	English
Author, co-author :	Crisanti, Cecilia [ > > ]
	Wallace, Africa [ > > ]
	Kapoor, Veena [ > > ]
	Vandermeers, Fabian [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
	Dowling, Melissa [ > > ]
	Pereira, Luana [ > > ]
	Coleman, Kara [ > > ]
	Campling, Barbara [ > > ]
	Fridlender, Zvi [ > > ]
	Kao, Gary [ > > ]
	Albelda, Steven [ > > ]
Publication date :	Aug-2009
Journal title :	Molecular Cancer Therapeutics
Publisher :	American Association for Cancer Research, Inc. (AACR)
Volume :	8
Issue/season :	8
Pages :	2221-2231
Audience :	International
ISSN :	1535-7163
e-ISSN :	1538-8514
City :	Philadelphia
Country :	PA
Abstract :	[en] Lung cancer is the leading cause of cancer deaths in the United States. Current therapies are inadequate. Histone deacetylase inhibitors (HDACi) are a recently developed class of anticancer agents that cause increased acetylation of core histones and nonhistone proteins leading to modulation of gene expression and protein activityin - volved in cancer cell growth and survival pathways. We examined the efficacyof the HDACi panobinostat (LBH589) in a wide range of lung cancers and mesotheliomas. Panobinostat was cytotoxic in almost all 37 cancer cell lines tested. IC50 and LD50 values were in the low nmol/L range (4–470 nmol/L; median, 20 nmol/L). Small cell lung cancer (SCLC) cell lines were among the most sensitive lines, with LD50 values consistently <25 nmol/L. In lung cancer and mesothelioma animal models, panobinostat significantlyde creased tumor growth byan average of 62% when compared with vehicle control. Panobinostat was equallye ffective in immunocompetent and severe combined immunodeficiencymic e, indicating that the inhibition of tumor growth by panobinostat was not due to direct immunologic effects.Panobinostat was, however, particularlyeffective in SCLC xenografts, and the addition of the chemotherapyag ent etoposide augmented antitumor effects. Protein analysis of treated tumor biopsies revealed elevated amounts of cell cycle regulators such as p21 and proapoptosis factors, such as caspase 3 and 7 and cleaved poly[ADP-ribose] polymerase, coupled with decreased levels of antiapoptotic factors such as Bcl-2 and Bcl-XL. These studies together suggest that panobinostat maybe a useful adjunct in the treatment of thoracic malignancies, especiallySCLC.
Permalink :	http://hdl.handle.net/2268/83490

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