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Histone Deacetylase Inhibitor MS-275 Inhibits Neuroblastoma Cell Growth by Inducing Cell Cycle Arrest, Apoptosis, Differentiation and by Targeting its Tumor Stem Cell Population

Objective: MS-275, a phase trialed histone deacetylase inhibitor will be characterized for its ability reduce neuroblastoma (NB) viability and to target the tumor stem cell (TSC) population in neuroblastoma.
Methods: Ability of MS-275 to reduce NB growth is characterized using a tumorigenic NB N-type cell line that has high differentiation potential. TSC enriched side population from NB and a reference teratocarcinoma cell line was analyzed as a model of TSC. The potential of MS-275 to modulate functional characteristics and markers of TSC was also investigated.
Results: MS-275 induces a G1 cell cycle arrest, the intrinsic apoptosis pathway in NB and can potentially differentiate NB into a more terminal phenotype. NB TSC-like population is reduced following MS-275 treatment by the targeting of their self-renewal and drug pumping ability.
Conclusions: By targeting both the NB and its TSC population, MS-275 has therapeutic potential for neuroblastoma. This warrants further in-vivo investigations.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OTU.1807/18968
Date16 February 2010
CreatorsTsui, Micky Ka Hon
ContributorsYeger, Herman
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
Languageen_ca
Detected LanguageEnglish
TypeThesis

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