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

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Ressource 1Download: Molecular Cancer 2008.pdf (1585.09 [Ko])
State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_D3898496EDEA
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 KB, Nardou K, Joseph JM, Gross N
Publication state
Published
Issued date
06/2008
Peer-reviewed
Oui
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.
Pubmed
Open Access
Yes
Create date
23/03/2020 11:44
Last modification date
26/06/2020 6:10
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