関: trichostatin、TSA

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the 1st letter of the Roman alphabet (同)a
the blood group whose red cells carry the A antigen (同)type_A, group A

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arsenicの化学記号

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/05/12 14:16:57」(JST)

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Trichostatin A (TSA) is an organic compound that serves as an antifungal antibiotic and selectively inhibits the class I and II mammalian histone deacetylase (HDAC) families of enzymes, but not class III HDACs (i.e., Sirtuins).^[1] TSA inhibits the eukaryotic cell cycle during the beginning of the growth stage. TSA can be used to alter gene expression by interfering with the removal of acetyl groups from histones (histone deacetylases, HDAC) and therefore altering the ability of DNA transcription factors to access the DNA molecules inside chromatin. It is a member of a larger class of histone deacetylase inhibitors (HDIs or HDACIs) that have a broad spectrum of epigenetic activities. Thus, TSA has some potential as an anti-cancer drug.^[2] One suggested mechanism is that TSA promotes the expression of apoptosis-related genes, leading to cancerous cells surviving at lower rates, thus slowing the progression of cancer.^[3] Other mechanisms may include the activity of HDIs to induce cell differentiation, thus acting to "mature" some of the de-differentiated cells found in tumors. HDIs have multiple effects on non-histone effector molecules, so the anti-cancer mechanisms are truly not understood at this time.

TSA inhibits HDACs 1, 3, 4, 6 and 10 with IC50 values around 20 nM.^[4]

TSA represses IL (interleukin)-1β/LPS (lipopolysaccharide)/IFNγ (interferon γ)-induced nitric oxide synthase (NOS)2 expression in murine macrophage-like cells but increases LPS-stimulated NOS2 expression in murine N9 and primary rat microglial cells.^[5]

However, there are few if any clinical trials of TSA.^[6]

References [edit]

^ Vanhaecke T, Papeleu P, Elaut G, Rogiers V (2004). "Trichostatin A-like hydroxamate histone deacetylase inhibitors as therapeutic agents: toxicological point of view". Curr Med Chem 11 (12): 1629–43. PMID 15180568.
^ Drummond DC, Noble CO, Kirpotin DB, Guo Z, Scott GK, Benz CC (2005). "Clinical development of histone deacetylase inhibitors as anticancer agents". Annu Rev Pharmacol Toxicol 45: 495–528. doi:10.1146/annurev.pharmtox.45.120403.095825. PMID 15822187.
^ Shankar S, Srivastava RK (2008). "Histone deacetylase inhibitors: mechanisms and clinical significance in cancer: HDAC inhibitor-induced apoptosis". Adv Exp Med Biol. Advances in Experimental Medicine and Biology 615: 261–98. doi:10.1007/978-1-4020-6554-5_13. ISBN 978-1-4020-6553-8. PMID 18437899.
^ http://www.freepatentsonline.com/y2009/0263353.html
^ Adcock (2007). "HDAC inhibitors as anti-inflammatory agents".
^ http://clinicaltrials.gov/ct2/results?term=Trichostatin+A

External links [edit]

Trichostatin_A Safety data sheet by Fermentek

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English Journal

The histone deacetylase inhibitor trichostatin A reduces lysosomal pH and enhances cisplatin-induced apoptosis.

Eriksson I, Joosten M, Roberg K, Ollinger K.SourceExperimental Pathology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Sweden.
Experimental cell research.Exp Cell Res.2013 Jan 1;319(1):12-20. doi: 10.1016/j.yexcr.2012.10.004. Epub 2012 Oct 12.
High activity of histone deacetylases (HDACs) has been documented in several types of cancer and may be associated with survival advantage. In a head and neck squamous cell carcinoma cell line, cisplatin-induced apoptosis was augmented by pretreatment with the HDAC inhibitor trichostatin A. Apoptosi
PMID 23063877

Trichostatin A induces apoptotic cell death of HeLa cells in a Bcl-2 and oxidative stress-dependent manner.

You BR, Park WH.SourceDepartment of Physiology, Medical School, Research Institute for Endocrine Sciences, Chonbuk National University, JeonJu 561-180, Republic of Korea.
International journal of oncology.Int J Oncol.2013 Jan;42(1):359-66. doi: 10.3892/ijo.2012.1705. Epub 2012 Nov 19.
Trichostatin A (TSA) as a HDAC inhibitor can regulate many biological properties including apoptosis and cell proliferation in various cancer cells. Here, we evaluated the effect of TSA on the growth and death of HeLa cervical cancer cells in relation to reactive
PMID 23165748

Japanese Journal

Epigenetic Status and Full-term Development of Bovine Cloned Embryos Treated with Trichostatin A

SAWAI Ken,FUJII Takashi,HIRAYAMA Hiroki,HASHIZUME Tsutomu,MINAMIHASHI Akira
The Journal of reproduction and development 58(3), 302-309, 2012-06-01
… We examined the comprehensive epigenetic status, including histone H3 and H4 acetylation, DNA methylation and level of mRNA transcripts of bovine somatic cell nuclear transfer (SCNT) embryos treated with trichostatin A (TSA), along with their full-term developmental efficacy. …
NAID 10030821159

Trichostatin A Improves Preimplantation Development of Bovine Cloned Embryos and Alters Expression of Epigenetic and Pluripotency Genes in Cloned Blastocysts

OH Hyun Ju,LEE Tae Hee,LEE Ji Hyun,LEE Byeong Chun
Journal of Veterinary Medical Science 74(11), 1409-1415, 2012
… We investigated the effects of exposure time and concentration of trichostatin A (TSA) on in vitro development and quality of bovine SCNT embryos. …
NAID 130001879729

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★リンクテーブル★

リンク元	「トリコスタチンA」「TSA」
関連記事	「A」「trichostatin」「Ad」

「トリコスタチンA」

Trichostatin A
Systematic (IUPAC) name
	7-[4-(dimethylamino)phenyl]-N-hydroxy-4,6-dimethyl-7-oxohepta-2,4-dienamide
Clinical data
Pregnancy cat.	D—teratogenic
Legal status	?
Identifiers
CAS number	58880-19-6
ATC code	None
PubChem	CID 444732
DrugBank	DB04297
ChemSpider	392575
ChEBI	CHEBI:46024
ChEMBL	CHEMBL99
Chemical data
Formula	C17H22N2O3
Mol. mass	302.37 g/mol
	SMILES O=C(NO)\C=C\C(=C\[C@H](C(=O)c1ccc(N(C)C)cc1)C)C;
	InChI InChI=1S/C17H22N2O3/c1-12(5-10-16(20)18-22)11-13(2)17(21)14-6-8-15(9-7-14)19(3)4/h5-11,13,22H,1-4H3,(H,18,20)/b10-5+,12-11+/t13-/m1/s1 ; Key:RTKIYFITIVXBLE-QEQCGCAPSA-N ;
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