Complex molecular mechanisms cooperate to mediate histone deacetylase inhibitors anti-tumour activity in neuroblastoma cells.
Complex molecular mechanisms cooperate to mediate histone deacetylase inhibitors anti-tumour activity in neuroblastoma cells.
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DOI：
10.1186/1476-4598-7-55
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发表时间：
2008-06-12
期刊：
影响因子：
37.3
通讯作者：
Gross N
中科院分区：
文献类型：
--
作者：
Mühlethaler-Mottet A;Meier R;Flahaut M;Bourloud KB;Nardou K;Joseph JM;Gross N
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. 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. 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.
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影响因子：
7.2
作者：
Flahaut, M;Mühlethaler-Mottet, A;Gross, N
通讯作者：
Gross, N
影响因子：
8
作者：
Hopkins-Donaldson, S;Yan, P;Gross, N
通讯作者：
Gross, N
DOI：
10.1073/pnas.172398399
发表时间：
2002-08-20
影响因子：
11.1
作者：
Kim, ES;Serur, A;Yamashiro, DJ
通讯作者：
Yamashiro, DJ
影响因子：
11.2
作者：
Huang, Xiangwei;Guo, Bin
通讯作者：
Guo, Bin
影响因子：
8
作者：
Deroanne, CF;Bonjean, K;Castronovo, V
通讯作者：
Castronovo, V