Actinomycin D is a chromopeptide antineoplastic antibiotic that exhibits high antibacterial and antitumor activity. Actinomycin D binds to single- and double-stranded DNA and subsequent inhibition of RNA and protein synthesis.
Actinomycin; Cosmegen; Cosmegen Lyovac; Dactinomycin; Lyovac Cosmegen
Soluble in water
0 mm Hg at 25 °C (est)
Mechanism Of Action
Good evidence exists that this drug bind strongly, but reversibly, to DNA, interfering with synthesis of RNA (prevention of RNA polymerase elongation) and, consequently, with protein synthesis.
Generally, the actinomycins exert an inhibitory effect on gram-positive and gram-negative bacteria and on some fungi. However, the toxic properties of the actinomycins (including dactinomycin) in relation to antibacterial activity are such as to preclude their use as antibiotics in the treatment of infectious diseases. Because the actinomycins are cytotoxic, they have an antineoplastic effect which has been demonstrated in experimental animals with various types of tumor implant. This cytotoxic action is the basis for their use in the treatment of certain types of cancer. Dactinomycin is believed to produce its cytotoxic effects by binding DNA and inhibiting RNA synthesis.
A dramatic decrease in anti-apoptotic myeloid leukemia cell differentiation protein (Mcl-1) mRNA and protein expression was detected upon actinomycin D treatment. Further, Mcl-l over-expression caused resistance to cell death upon treatment with actinomycin D, implicating a role for the down-regulation of Mcl-1 in actinomycin D-induced apoptosis. Actinomycin D sensitized cells to ABT-737 treatment in a Bak- or Bax-dependent manner. Importantly, low concentrations of actinomycin D and ABT-737 were more effective in inducing cell death in transformed cells than their untransformed counterparts. A synergistic effect of actinomycin D and ABT-737 on cell death was observed in several human tumor cell lines. Like actinomycin D treatment, knocking down Mcl-1 expression greatly sensitized tumor cells to ABT-737, and Mcl-1 over-expression abrogated the cytotoxic effect induced by ABT-737 and actinomycin D. These results suggest that the down-regulation of Mcl-1 by actinomycin D is likely responsible for the observed synergistic effect between the two drugs.
In an in vivo study, the pluronic gel containing 80 nM and 80 microM actinomycin D was applied topically to surround the rat carotid adventitia; the thickness of neointima was substantially reduced (45 and 55%, respectively). The protein expression levels of proliferating cell nuclear antigen (PCNA), focal adhesion kinase (FAK), and Raf were all suppressed by actinomycin D. Extracellular signal-regulated kinases (Erk) involved in cell-cycle arrest were found to increase by actinomycin D.
Clinical Trial Information
|NCT Number||Condition Or Disease||Phase||Start Date||Sponsor||Status|
|NCT00003688||Gestational Trophoblastic Tumor||Phase 2||2013-06-10||Gynecologic Oncology Group||Completed|
|NCT01823315||Gestational Trophoblastic Disease||Phase 3||2019-12-24||Ding Ma||Active, not recruiting|
|NCT00075582||Adult Rhabdomyosarcoma||Phase 3||2021-11-19||Children's Oncology Group||Completed|
|NCT04562558||Gestational Trophoblastic Tumor||Not Applicable||2021-11-16||xiang yang||Recruiting|
|NCT00900354||Unspecified Childhood Solid Tumor, Protocol Specific||2013-08-12||Children's Cancer and Leukaemia Group||Unknown Verified June 2009 by National Cancer Institute (NCI). Recruitment status was Recruiting|
Red Crystalline Powder
Dilute soln are very sensitive to light /Trihydrate/;Soln should not be exposed to direct sunlight
Acute Toxic; Health Hazard
1386°C at 760 mmHg