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Systematic Analysis of Time-Series Gene Expression Data on Tumor Cell-Selective Apoptotic Responses to HDAC Inhibitors

SAHA (suberoylanilide hydroxamic acid or vorinostat) is the first nonselective histone deacetylase (HDAC) inhibitor approved by the US Food and Drug Administration (FDA). SAHA affects histone acetylation in chromatin and a variety of nonhistone substrates, thus influencing many cellular processes. I...

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Detalles Bibliográficos
Autores principales: Qi, Yun-feng, Huang, Yan-xin, Dong, Yan, Zheng, Li-hua, Bao, Yong-li, Sun, Lu-guo, Wu, Yin, Yu, Chun-lei, Jiang, Hong-yu, Li, Yu-xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4211306/
https://www.ncbi.nlm.nih.gov/pubmed/25371703
http://dx.doi.org/10.1155/2014/867289
Descripción
Sumario:SAHA (suberoylanilide hydroxamic acid or vorinostat) is the first nonselective histone deacetylase (HDAC) inhibitor approved by the US Food and Drug Administration (FDA). SAHA affects histone acetylation in chromatin and a variety of nonhistone substrates, thus influencing many cellular processes. In particularly, SAHA induces selective apoptosis of tumor cells, although the mechanism is not well understood. A series of microarray experiments was recently conducted to investigate tumor cell-selective proapoptotic transcriptional responses induced by SAHA. Based on that gene expression time series, we propose a novel framework for detailed analysis of the mechanism of tumor cell apoptosis selectively induced by SAHA. Our analyses indicated that SAHA selectively disrupted the DNA damage response, cell cycle, p53 expression, and mitochondrial integrity of tumor samples to induce selective tumor cell apoptosis. Our results suggest a possible regulation network. Our research extends the existing research.