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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

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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. 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
3. 肝疾患を有する患者における化学療法による肝毒性および用量調整 chemotherapy hepatotoxicity and dose modification in patients with liver disease
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. 小児、思春期および成人期の横紋筋肉腫：治療 rhabdomyosarcoma in childhood adolescence and adulthood treatment

English Journal

The use of isolated limb infusion in limb threatening extremity sarcomas.

Vohra NA, Turaga KK, Gonzalez RJ, Conley A, Reed D, Bui MM, Cheong D, Letson DG, Zager JS.SourceDepartment of Sarcoma Oncology, Moffitt Cancer Center , Tampa , Florida.
International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.Int J Hyperthermia.2012 Dec 3. [Epub ahead of print]
This paper reports a single-institution experience with the use of isolated limb infusion for limb salvage in locally advanced, unresectable, recurrent limb threatening soft tissue sarcomas. Background: Locally advanced, limb threatening soft tissue sarcomas (STS) pose a significant treatment chal
PMID 23205633

What is New in Rhabdomyosarcoma Management in Children?

Gosiengfiao Y, Reichek J, Walterhouse D.SourceAnn and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Division of Hematology/Oncology/Stem Cell Transplant, Chicago, IL, USA.
Paediatric drugs.Paediatr Drugs.2012 Dec 1;14(6):389-400. doi: 10.2165/11599440-000000000-00000.
Optimal management of rhabdomyosarcoma requires establishing the correct pathologic diagnosis, histologic sub-type, primary site, extent of disease (Stage), and extent of resection (Group). Based on these features, cooperative groups in North America and Europe have defined risk-adapted treatments t
PMID 23050743

Japanese Journal

A Clinical Study on Parotid Tumors in Children and Adolescents

Hori Ryusuke,Shoji Kazuhiko,Hamaguchi Kiyomi,Okanoue Yusuke,Fujimura Shintaro,Wakizaka Hitomi
耳鼻咽喉科臨床　補冊 137(0), 58-59, 2013
… According to the Intergroup Rhabdomyosarcoma Study-IV, which was mostly used for the treatment of rhabdomyosarcoma, chemotherapy using vincristine, dactinomycin, and cyclophosphamide was performed as a postoperative treatment. …
NAID 130004558717

臨床小児・若年者耳下腺腫瘍の検討

堀龍介,庄司和彦,濱口清海 [他],岡上雄介,藤村真太郎,脇坂仁美
耳鼻咽喉科臨床 106(1), 23-28, 2013
… According to the Intergroup Rhabdomyosarcoma Study-IV, which was mostly used for the treatment of rhabdomyosarcoma, chemotherapy using vincristine, dactinomycin, and cyclophosphamide was performed as a postoperative treatment. …
NAID 130003373993

副腎癌との鑑別が困難だった後腹膜Ewing肉腫の1例

佐藤真彦,宮里実,山田成幸 [他]
泌尿器科紀要 57(6), 303-307, 2011-06
… Considering it a high risk, we started adjuvant VAIA(vincristine, dactinomycin, ifosfamide, and doxorubicin) chemotherapy soon after the operation. …
NAID 40018861642

Related Pictures

★リンクテーブル★

リンク元	「絨毛癌」「アクチノマイシンD」「抗悪性腫瘍薬」「Cosmegen」

「絨毛癌」

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); ;
Routes of; administration	IV
Legal status
Legal status	AU: S4 (Prescription only); CA: ℞-only; UK: POM (Prescription only); US: ℞-only;
Pharmacokinetic data
Protein binding	5%
Biological half-life	36 hours
Identifiers
CAS Number	50-76-0
ATC code	L01DA01 (WHO)
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
Molar 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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