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Curcumin HAT inhibitory activity correlation with its anti -tumor activity

Author: ZhaoJinYan
Tutor: WangZuo;ChenXiaoGuang;FuZhaoZuo
School: Peking Union Medical College , China
Course: Pharmacology
Keywords: Curcumin Histone Histone acetyltransferase p21CIP/WAF1 ROS
CLC: R285.5
Type: Master's thesis
Year: 2008
Downloads: 75
Quote: 0
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Abstract


Curcumin (Curcumin) is a polyphenolic substances can inhibit a variety of tumor cell growth in vitro and in vivo tumor occurs in cancer prevention and treatment has great potential for development. Histone acetyltransferase (Histoneacetyltransferase, HAT) and histone deacetylase (Histone deacetylase, HDAC) the regulation of core histone acetylation state. HAT overexpression can raise a variety of transcription factors, leading to abnormal gene expression, causing tumors or other diseases. Recent studies have reported that curcumin is a typical HAT inhibitors, inhibit the activity of anti-tumor effect of curcumin HAT discussed. HDAC activity in vitro enzymatic detection, curcumin had no effect, while SAHA significantly inhibited HDAC activity, IC 50 for 0.41μM; curcumin has good HAT inhibitory activity, IC 50 53μM. In the cytotoxicity assays, curcumin inhibit a variety of tumor cell growth, IC 50 the range of 5 to 30 μm. HDAC inhibitors SAHA also inhibit the growth of a variety of tumor cells, IC 50 the range is 0.45 to 3.86μM. Using probability and law calculated The curcumin and SAHA joint application interaction on the level of cytotoxic combination of curcumin 0.33μM SAHA performance by simply adding or antagonistic effects; performance combined with 1μM SAHA antagonism effect. At the protein level, curcumin and SAHA promote cell histone acetylation, but the role of curcumin weak. , Histone acetylation levels showed additive or synergistic the curcumin and SAHA joint application. Using semi-quantitative RT-PCR method to detect p21 CIP/WAF1 mRNA expression, curcumin and SAHA could stimulate cells of p21 CIP/WAF1 mRNA expression, high concentrations of callus were 1.3 to 1.8 times and 3 to 6 times. The combination of the two drugs performance to antagonistic SAHA induced p21 CIP/WAF1 for curcumin mRNA expression, interaction index (CDI) is less than 0.85. Flow cytometry showed that curcumin and SAHA can induce the cells to produce ROS (Reactive OxygenSpecies, reactive oxygen species); combination of the two drugs, curcumin significantly antagonized SAHA-induced ROS production. These results suggest that curcumin HAT inhibitory activity of HDAC activity in vitro. Slightly promote histone acetylation at the cellular level, to promote p21 CIP/WAF1 mRNA expression level of gene expression, tumor cells induced by ROS levels increase. In histone acetylation levels of performance for additive or synergistic, antagonistic SAHA induced p21 CIP/WAF1 mRNA expression, while antagonistic to SAHA-induced ROS production the curcumin and SAHA joint application. We think that the anti-tumor effect of curcumin, its HAT inhibition activity and induction of histone acetylation relationship.

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