Actinomycin D (Synonyms: Cosmegen, Dactinomycin, Meractinomycin, NCI C04682, NSC 3053, Oncostatin K)

Actinomycin D (dactinomycin) is a natural chromopeptide isolated from Streptomyces species, and has one heterocyclic chromophore and two cyclic pentapeptide lactone rings. [1] It is the first antibiotic showing anti-tumor activity, and has been implemented in the clinical practice for years to treat, such as testicular cancer, and choriocarcinoma.[2]

Actinomycin D intercalates into DNA to inhibit the transcription. It forms a very stable complex with DNA, preventing the unwinding of the DNA double-helix, so as to inhibit the DNA-dependent RNA polymerase activity. Actinomycin D is well implemented in mRNA stability assays to inhibit the synthesis of new mRNA, allowing the assessment of mRNA decay by measuring mRNA abundance following transcription inhibition. [3]

The in vitro experiment suggests that actinomycin D is an potent and effective agent to inhibit the proliferation of SMC by preventing cells from getting into S phase. The LD50 (260 lM) determined by measuring the remaining viable cells at various concentrations of actinomycin D was about five orders greater than that of IC50 (0.4 nM), which was calculated by measuring the percentage of cells in S phase following the treatment of actinomycin D. A dose-dependent inhibition by actinomycin D was found in PCNA, Raf and FAK. However, in contrast to those seen on PCNA, Raf and FAK expression, the phosphorylated Erk was significantly up-regulated by actinomycin D. An in vivo study using rat carotid artery as a model was conducted to evaluate if topically applied actinomycin D onto the arterial adventitia of the artery was effective in suppressing the formation of stenosis following a balloon angioplasty. Topical application of pluronic gel containing 80 nM and 80 μM actinomycin D to surround the adventitia of rat carotid arteries, the thickness of the neointima was significantly reduced (45% and 55%, respectively). [4]

Reference:
[1]. Farber S. Chemotherapy in the treatment of leukemia and Wilms' tumor. JAMA. 1966 Nov 21;198(8):826-36. PMID: 4288581.
[2]. Lewis J.L., Jr. Chemotherapy of gestational choriocarcinoma. Obstet. Gynecol. Surv. 1973;28:7478–7480. doi: 10.1097/00006254-197307000-00006.
[3]. Shyu A. B., Greenberg M. E. and Belasco J. G.(1989). The c-fos transcript is targeted for rapid decay by two distinct mRNA degradation pathways. Genes Dev 3(1): 60-72.
[4]. Wu, C. H., Pan, J. S., Chang, W. C., Hung, J. S., & Mao, S. J. T. (2005). The molecular mechanism of actinomycin D in preventing neointimal formation in rat carotid arteries after balloon injury. Journal of Biomedical Science, 12(3), 503–512. doi:10.1007/s11373-005-6900-5.