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the 4th letter of the Roman alphabet (同)d
any of various red antibiotics isolated from soil bacteria

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deuteriumの化学記号
(おもに人称代名詞・固有名詞(人名),thereの後で)had, wouldの短縮形 / (疑問文でwhere,what,whenの後で)didの短縮形;Where'd he go?=Where did he go?

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/01/17 17:38:53」(JST)

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Dactinomycin. also known as actinomycin D, is the most significant member of actinomycines, which are a class of polypeptide antitumor antibiotics isolated from soil bacteria of the genus Streptomyces.^[1] It is one of the older anticancer drugs, and has been used for many years.

It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.^[2]

Medical use

Actinomycin is a clear, yellow liquid administered intravenously and most commonly used in treatment of a variety of cancers, including:

Gestational trophoblastic neoplasia^[3]
Wilms' tumor^[4]
Rhabdomyosarcoma^[5]
Ewing's sarcoma^[6]
Malignant hydatidiform mole^[7]

Sometimes it will be combined with other drugs in Chemotherapy regimens, like the VAC regimen (with Vincristine and Cyclophosphamide) for treating rhabdomyosarcoma and Ewing's Sarcoma.

It is also used as a radiosensitizer in adjunct to radiotherapies, since it can increase the radiosensitivity of tumor cells by inhibiting repair of sublethal radiation damage and delay the onset of the compensatory hyperplasia that occurs following irradiation.^[8]

Side effects

Common adverse drug reaction includes bone marrow suppression, fatigue, hair loss, mouth ulcer, loss of appetite and diarrhea. Actinomycin is a vesicant, if extravasation occurs.

Mechanism

In cell biology, Actinomycin D is shown to have the ability to inhibit transcription. Actinomycin D does this by binding DNA at the transcription initiation complex and preventing elongation of RNA chain by RNA polymerase.^[9]

History

Actinomycin D was the first antibiotic shown to have anti-cancer activity.^[1] It was first isolated by Selman Waksman and his co-worker H. B. Woodruff in 1940.^[10] It was approved by the U.S. Food and Drug Administration (FDA) on December 10, 1964 and launched by Merck Sharp and Dohme under the trade name Cosmegen.

Research use

Because Actinomycin can bind DNA duplexes, it can also interfere with DNA replication, although other chemicals such as hydroxyurea are better suited for use in the laboratory as inhibitors of DNA synthesis.

Actinomycin D and its fluorescent derivative, 7-aminoactinomycin D (7-AAD), are used as stains in microscopy and flow cytometry applications. The affinity of these stains/compounds for GC-rich regions of DNA strands makes them excellent markers for DNA. 7-AAD binds to single stranded DNA; therefore it is a useful tool in determining apoptosis and distinguishing between dead cells and live ones.^[11]

References

^ ^a ^b Hollstein, U. (1974). "Actinomycin. Chemistry and mechanism of action". Chemical Reviews 74 (6): 625–652. doi:10.1021/cr60292a002.
^ "19th WHO Model List of Essential Medicines (April 2015)" (PDF). WHO. April 2015. Retrieved May 10, 2015.
^ Turan T, Karacay O, Tulunay G, Boran N, Koc S, Bozok S, Kose M (2006). "Results with EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) chemotherapy in gestational trophoblastic neoplasia". Int J Gynecol Cancer 16 (3): 1432–8. doi:10.1111/j.1525-1438.2006.00606.x. PMID 16803542.
^ D'Angio GJ, Evans A, Breslow N, Beckwith B, Bishop H, Farewell V, Goodwin W, Leape L, Palmer N, Sinks L, Sutow W, Tefft M, Wolff J (1981). "The treatment of Wilms' tumor: results of the Second National Wilms' Tumor Study.". Cancer 47 (9): 2302–11. doi:10.1002/1097-0142(19810501)47:9<2302::aid-cncr2820470933>3.0.co;2-k. PMID 6164480.
^ Khatua S, Nair C, Ghosh K (2004). "Immune-mediated thrombocytopenia following dactinomycin therapy in a child with alveolar rhabdomyosarcoma: the unresolved issues". J Pediatr Hematol Oncol 26 (11): 777–9. doi:10.1097/00043426-200411000-00020. PMID 15543019.
^ Jaffe, N.; Paed, D.; Traggis, D.; Salian, S.; Cassady, J. R. (1976). "Improved outlook for Ewing's sarcoma with combination chemotherapy (vincristine, actinomycin D and cyclophosphamide) and radiation therapy". Cancer 38 (5): 1925–1930. doi:10.1002/1097-0142(197611)38:5<1925::AID-CNCR2820380510>3.0.CO;2-J. PMID 991106.
^ Uberti, E. M. H.; Fajardo, M. D. C.; Ferreira, S. V. V. R.; Pereira, M. C. V.; Seger, R. C.; Moreira, M. A. L. R.; Torres, M. D.; De Nápoli, G.; Schmid, H. (2009). "Reproductive outcome after discharge of patients with high-risk hydatidiform mole with or without use of one bolus dose of actinomycin D, as prophylactic chemotherapy, during the uterine evacuation of molar pregnancy". Gynecologic Oncology 115 (3): 476–481. doi:10.1016/j.ygyno.2009.09.012. PMID 19818481.
^ Hagemann, R. F.; Concannon, J. P. (1973). "Mechanism of intestinal radiosensitization by actinomycin D". British Journal of Radiology 46 (544): 302–308. doi:10.1259/0007-1285-46-544-302. PMID 4720744.
^ Sobell H (1985). "Actinomycin and DNA transcription". Proceedings of the National Academy of Sciences of the United States of America 82 (16): 5328–31. doi:10.1073/pnas.82.16.5328. PMC 390561. PMID 2410919.
^ Waksman S A, Woodruff H B (1940). "Bacteriostatic and bacteriocidal substances produced by soil actinomycetes". Proc Soc Exper Biol 45: 609–614.
^ Toba, K.; Koike, T.; Watanabe, K.; Fuse, I.; Takahashi, M.; Hashimoto, S.; Takahashi, H.; Abe, T.; Yano, T.; Shibazaki, Y.; Itoh, H.; Aizawa, Y. (2000). "Cell kinetic study of normal humanbone marrow hematopoiesis andacute leukemia using 7AAD/PY". European Journal of Haematology 64 (1): 10–21. doi:10.1034/j.1600-0609.2000.09005.x. PMID 10680701.

External links

MedlinePlus DrugInfo medmaster-a682224

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 低リスク妊娠性絨毛腫瘍の初期マネージメント initial management of low risk gestational trophoblastic neoplasia
2. ユーイング肉腫ファミリーの腫瘍の治療 treatment of the ewing sarcoma family of tumors
3. 抵抗性または再発性の妊娠性絨毛腫瘍のマネージメント management of resistant or recurrent gestational trophoblastic neoplasia
4. 高リスク妊娠性絨毛腫瘍の初期マネージメント initial management of high risk gestational trophoblastic neoplasia
5. ウィルムス腫瘍の治療および予後 treatment and prognosis of wilms tumor

English Journal

Involvement of JNK and NF-κB pathways in lipopolysaccharide (LPS)-induced BAG3 expression in human monocytic cells.

Wang HQ, Meng X, Liu BQ, Li C, Gao YY, Niu XF, Li N, Guan Y, Du ZX.SourceDepartment of Biochemistry & Molecular Biology, China Medical University, Shenyang 110001, China; Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110001, China.
Experimental cell research.Exp Cell Res.2012 Jan 1;318(1):16-24. Epub 2011 Oct 12.
Lipopolysaccharide (LPS) is an outer-membrane glycolipid component of Gram-negative bacteria known for its fervent ability to activate monocytic cells and for its potent proinflammatory capabilities. Bcl-2-associated athanogene 3 (BAG3) is a survival protein that has been shown to be stimulated duri
PMID 22020323

Spectroscopic studies of dactinomycin and vinorelbine binding to deoxyribonucleic acid and chromatin.

Rabbani-Chadegani A, Keyvani-Ghamsari S, Zarkar N.SourceDepartment of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. rabbani@ibb.ut.ac.ir
Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.Spectrochim Acta A Mol Biomol Spectrosc.2011 Dec 15;84(1):62-7. Epub 2011 Sep 6.
Dactinomycin and vinorelbine are anticancer drugs, widely used as chemotherapeutic agents for the treatment of various cancers. This study represents an attempt to compare the effect of these drugs on DNA and soluble chromatin employing UV/vis, fluorescence and circular dichroism spectroscopy techni
PMID 21981942

Japanese Journal

症例選択的Actinomycin-D動注療法およびUAEにより治療し得た子宮頸管妊娠の1例

伊勢由香里,國久有香,上田智弘 [他]
臨床婦人科産科 66(6), 495-499, 2012-05
NAID 40019330721

A long-term survival case of adult undifferentiated embryonal sarcoma of liver

Noguchi Keita,Yokoo Hideki,Nakanishi Kazuaki,Kakisaka Tatsuhiko,Tsuruga Yosuke,Kamachi Hirofumi,Matsushita Michiaki,Kamiyama Toshiya
World Journal of Surgical Oncology 10, 65, 2012-04-27
… Adjuvant therapy with cisplatin, vincristine, doxorubicin, cyclophosphamide, and actinomycin D was initiated. …
NAID 120004608971

Related Pictures

★リンクテーブル★

リンク元	「細胞死」「アクチノマイシンD」「Cosmegen」
関連記事	「D」「actinomycin」

「細胞死」

Dactinomycin
Systematic (IUPAC) name
	2-Amino-N,N′- bis[(6S,9R,10S,13R,18aS)-6,13-diisopropyl-2,5,9-trimethyl-1,4,7,11,14-pentaoxohexadecahydro-1H-pyrrolo[2,1-i][1,4,7,10,13]oxatetraazacyclohexadecin-10-yl]-4,6-dimethyl-3-oxo-3H-phenoxazine-1,9-dicarboxamide
Clinical data
Trade names	Cosmegen
AHFS/Drugs.com	monograph
MedlinePlus	a682224
Pregnancy; category	AU: D; US: D (Evidence of risk); ;
Legal status	AU: S4 (Prescription only); CA: ℞-only; UK: POM (Prescription only); US: ℞-only;
Routes of; administration	IV
Pharmacokinetic data
Protein binding	5%
Biological half-life	36 hours
Identifiers
CAS Number	50-76-0
ATC code	L01DA01
PubChem	CID: 2019
DrugBank	DB00970
ChemSpider	10482167
UNII	1CC1JFE158
KEGG	C06770
ChEBI	CHEBI:27666
ChEMBL	CHEMBL1554
NIAID ChemDB	009885
Synonyms	Actinomycin D; 2-Amino- 4,6-dimethyl- 3-oxo- 3H-phenoxazine- 1,9-dicarboxylic acid bis- [(5,12-diisopropyl- 9,13,16-trimethyl- 4,7,11,14,17-pentaoxo- hexadecahydro- 10-oxa- 3a,6,13,16-tetraaza- cyclopentacyclohexadecen- 8-yl)- amide]
Chemical data
Formula	C62H86N12O16
Molecular mass	1255.42 g/mol
	InChI InChI=1S/C62H86N12O16/c1-27(2)42-59(84)73-23-17-19-36(73)57(82)69(13)25-38(75)71(15)48(29(5)6)61(86)88-33(11)44(55(80)65-42)67-53(78)35-22-21-31(9)51-46(35)64-47-40(41(63)50(77)32(10)52(47)90-51)54(79)68-45-34(12)89-62(87)49(30(7)8)72(16)39(76)26-70(14)58(83)37-20-18-24-74(37)60(85)43(28(3)4)66-56(45)81/h21-22,27-30,33-34,36-37,42-45,48-49H,17-20,23-26,63H2,1-16H3,(H,65,80)(H,66,81)(H,67,78)(H,68,79)/t33-,34-,36+,37+,42-,43-,44+,45+,48+,49+/m1/s1 ; Key:RJURFGZVJUQBHK-IIXSONLDSA-N ;
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　　[★]

英: cell death
関: アポトーシス、プログラム細胞死、ネクローシス

アポトーシスとネクローシスの違い

	アポトーシス	ネクローシス
形態	濃縮、分断化	溶解
膜の強度	保たれる	失われる
ミトコンドリア	影響を受けない	膨潤、Ca取り込み
クロマチン	偏在化、濃縮	凝集
タンパク質合成阻害	死が阻害されうる・actinomycin D ・CHX	なし
原因	糖質コルチコイド、ホルモン刺激の低下、過剰な刺激、中程度の毒	強い毒、低酸素、pHの大きな変動
典型例	胸腺←糖質コルチコイド	肝臓←肝毒性物質
細胞の変化	リソソームは変化無し	リソソームが破裂する
核の変化	特定の長さに切断	ランダムに切断
最初の徴候	エンドヌクレアーゼの活性化	小疱形成、膨潤