Background
Histone acetyltransferase and histone deacetylase (HDAC) activity regulates the reversible acetylation of lysine residues within histone tails, which results in either transcriptional activation or repression of nearby genes. Compounds that modulate this activity are of interest in cancer chemotherapeutics as well as for treating psychiatric disorders, malaria, and other diseases. Apicidin is a fungal toxin that has broad spectrum activity against Apicomplexan parasites through inhibiting HDACs (IC50 = 0.7 nM).[1] An in vitro activity assay demonstrates apicidin inhibition of HDAC3/NCoR, a class I HDAC, at a much higher potency than for class II HDAC6 (IC50s = 15.8 and 665.1 nM, respectively).[2] Apicidin exhibits antiproliferative activity against various cancer cell lines (IC50s = 0.13-2.36 μM), and at 0.5 – 2 μM it induces selective changes in p21WAF1/Cip1 and gelsolin gene expression, which control cell cycle and cell morphology, respectively.[3]
组蛋白乙酰转移酶和组蛋白去乙酰化酶（HDAC）活性可以调节组蛋白尾部中赖氨酸残基的可逆乙酰化，从而导致附近基因的转录激活或抑制。调节这种活性的化合物对于癌症化学治疗以及治疗精神障碍、疟疾和其他疾病具有重要意义。Apicidin是一种真菌毒素，对孢子虫具有广谱活性，通过抑制HDACs（IC50=0.7 nM）实现。一项体外活性测定表明，Apicidin对类I HDAC3/NCoR的抑制效力远高于对类II HDAC6的抑制效力（IC50分别为15.8和665.1 nM）。Apicidin对多种癌细胞系具有抗增殖活性（IC50为0.13-2.36 μM），在0.5-2 μM时它会引起p21WAF1/Cip1和gelsolin基因表达的选择性改变，这些基因分别控制细胞周期和细胞形态。
Reference:
[1]. Darkin-Rattray, S.J., Gurnett, A.M., Myers, R.W., et al. Apicidin: A novel antiprotozoal agent that inhibits parasite histone deacetylase. Proceedings of the National Academy of Sciences of the United States of America 93(23), 13143-13147 (1996).
[2]. Mazitschek, R., Patel, V., Wirth, D.F., et al. Development of a fluorescence polarization based assay for histone deacetylase ligand discovery. Bioorg. Med. Chem. Lett. 18(9), 2809-2812 (2008).
[3]. Han, J.W., Ahn, S.H., Park, S.H., et al. Apicidin, a histone deacetylase inhibitor, inhibits proliferation of tumor cells via induction of p21WAF1/Cip1 and gelsolin. Cancer Research 60, 6068-6074 (2000).
Protocol
| Cell experiment [1]: |
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Cell lines
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HeLa cells
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Preparation method
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The solubility of this compound in DMSO is limited. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20 °C for several months.
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Reaction Conditions
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1 μg/mL; 24 hrs
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Applications
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Apicidin exhibited long-lasting anti-proliferative activity against HeLa cells, up to 48 hrs after withdrawal.
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| Animal experiment [2]: |
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Animal models
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Ishikawa endometrial cancer xenografted mouse model
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Dosage form
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5 mg/kg; i.p.; q.d., for 21 days
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Applications
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Significant inhibition of tumor growth was observed starting from day 15 after the Apicidin treatment. Apicidin (5 mg/kg) significantly inhibited tumor growth up to 53%.
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Other notes
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Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
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参考文献:
[1]. Han JW, Ahn SH, Park SH, Wang SY, Bae GU, Seo DW, et al. Apicidin, a histone deacetylase inhibitor, inhibits proliferation of tumor cells via induction of p21WAF1/Cip1 and gelsolin. Cancer Res 2000,60:6068-6074.
[2]. Ahn MY, Chung HY, Choi WS, Lee BM, Yoon S, Kim HS. Anti-tumor effect of apicidin on Ishikawa human endometrial cancer cells both in vitro and in vivo by blocking histone deacetylase 3 and 4. Int J Oncol 2010,36:125-131.
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