Comput Math Methods Med - Systematic analysis of time-series gene expression data on tumor cell-selective apoptotic responses to HDAC inhibitors.

Tópicos

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Resumo

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.

Resumo Limpo

saha suberoylanilid hydroxam acid vorinostat first nonselect histon deacetylas hdac inhibitor approv us food drug administr fda saha affect histon acetyl chromatin varieti nonhiston substrat thus influenc mani cellular process particular saha induc select apoptosi tumor cell although mechan well understood seri microarray experi recent conduct investig tumor cellselect proapoptot transcript respons induc saha base gene express time seri propos novel framework detail analysi mechan tumor cell apoptosi select induc saha analys indic saha select disrupt dna damag respons cell cycl p express mitochondri integr tumor sampl induc select tumor cell apoptosi result suggest possibl regul network research extend exist research

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