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Background
IC50: Actinomycin D showed a concentration-dependent decrease of DNA repair activity with the IC50 of 0.42 μM [1].Actinomycin D (dactinomycin), a member of actinomycines, which are a class of polypeptide antibiotics isolated from soil bacteria of the genus Streptomyces. Have been used for many years as an older chemotherapy, actinomycin D binds to double- and single-stranded DNA to inhibit DNA and RNA synthesis by binding DNA at the transcription initiation complex and preventing elongation of RNA chain by RNA polymerase. In vitro: A previous study was designed to determine the effects of actinomycin D on leptin release by isolated rat adipocytes during primary culture for 24 hr. Results showed that both actinomycin D and dexamethasone reduced the loss of leptin mRNA seen over the 24-hr incubation. Maximal effects on leptin release and leptin mRNA accumulation required only 0.1 μM of actinomycin D, a concentration that had no significant effect on the 18S RNA content of adipocytes at the end of a 24-hr incubation. In contrast to the reduced loss of leptin mRNA seen at 24 hr, the loss of glyceraldehyde-3-phosphate dehydrogenase messenger ribonucleic acid (GAPDH mRNA) was enhanced in the presence of 0.1 μM of actinomycin D. These results demonstrated a unique regulation of leptin release and leptin mRNA levels by actinomycin D [2]. In vivo: A rat in vivo study showed that the effect of actinomycin D on the time course of the population spike potentiation was more pronounced than the effect on the time course of the EPSP component, suggesting different mechanisms for the two forms of potentiation. Moreover, both intrahippocampal and intracerebroventricular injection of actinomycin D prevented a late stage of LTP in the dentate gyrus in vivo measured as the population spike amplitude [3]. Clinical trial: Actinomycin is intravenously administered and most commonly used in the treatment of a variety of cancers, including gestational trophoblastic neoplasia, wilms' tumor, rhabdomyosarcoma, ewing's sarcoma and malignant hydatidiform mole. Combined with other drugs in chemotherapy regimens, such as the VAC regimen, it will be used for treating rhabdomyosarcoma and Ewing's Sarcoma. In addition, it is also used as a radiosensitizer in adjunct to radiotherapies, as it increases the tumor cells radiosensitivity.
[1] Barret JM, Salles B, Provot C, Hill BT. Evaluation of DNA repair inhibition by antitumor or antibiotic drugs using a chemiluminescence microplate assay. Carcinogenesis. 1997 ;18(12):2441-5.
[2] Fain JN, Bahouth SW. Stimulation of leptin release by actinomycin D in rat adipocytes. Biochem Pharmacol. 1998;55(8):1309-14.
[3] Frey U, Frey S, Schollmeier F, Krug M. Influence of actinomycin D, a RNA synthesis inhibitor, on long-term potentiation in rat hippocampal neurons in vivo and in vitro. J Physiol. 1996;490(Pt 3):703-11.
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