Complex molecular mechanisms cooperate to mediate histone deacetylase inhibitors anti-tumour activity in neuroblastoma cells

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Serval ID
serval:BIB_E298790DD539
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Complex molecular mechanisms cooperate to mediate histone deacetylase inhibitors anti-tumour activity in neuroblastoma cells
Journal
Molecular Cancer
Author(s)
Mühlethaler-Mottet A., Meier R., Flahaut M., Bourloud K.B., Nardou K., Joseph J.M., Gross N.
ISSN
1476-4598
Publication state
Published
Issued date
2008
Peer-reviewed
Oui
Volume
7
Number
55
Pages
1-12
Language
english
Abstract
BACKGROUND: Histone deacetylase inhibitors (HDACi) are a new class of promising anti-tumour agent inhibiting cell proliferation and survival in tumour cells with very low toxicity toward normal cells. Neuroblastoma (NB) is the second most common solid tumour in children still associated with poor outcome in higher stages and, thus NB strongly requires novel treatment modalities. RESULTS: We show here that the HDACi Sodium Butyrate (NaB), suberoylanilide hydroxamic acid (SAHA) and Trichostatin A (TSA) strongly reduce NB cells viability. The anti-tumour activity of these HDACi involved the induction of cell cycle arrest in the G2/M phase, followed by the activation of the intrinsic apoptotic pathway, via the activation of the caspases cascade. Moreover, HDACi mediated the activation of the pro-apoptotic proteins Bid and BimEL and the inactivation of the anti-apoptotic proteins XIAP, Bcl-xL, RIP and survivin, that further enhanced the apoptotic signal. Interestingly, the activity of these apoptosis regulators was modulated by several different mechanisms, either by caspases dependent proteolytic cleavage or by degradation via the proteasome pathway. In addition, HDACi strongly impaired the hypoxia-induced secretion of VEGF by NB cells. CONCLUSION: HDACi are therefore interesting new anti-tumour agents for targeting highly malignant tumours such as NB, as these agents display a strong toxicity toward aggressive NB cells and they may possibly reduce angiogenesis by decreasing VEGF production by NB cells.
Keywords
Antibiotics, Antineoplastic, Antineoplastic Agents, Apoptosis, Apoptosis Regulatory Proteins, Butyrates, Caspases, Cell Cycle, Cell Hypoxia, Cell Line, Tumor, Cell Proliferation, Cell Survival, Dose-Response Relationship, Drug, Doxorubicin, Enzyme Inhibitors, Histone Deacetylases, Humans, Hydroxamic Acids, Neuroblastoma, Time Factors, Vascular Endothelial Growth Factor A
Pubmed
Web of science
Open Access
Yes
Create date
22/01/2009 13:33
Last modification date
20/08/2019 16:06
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