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 Dactinomycin

dactinomycin is a chromopeptide antineoplastic antibiotic isolated from the bacterium Streptomyces parvulus. Dactinomycin intercalates between adjacent guanine-cytosine base pairs, blocking the transcription of DNA by RNA polymerase; it also causes single-strand DNA breaks, possibly via a free-radical intermediate or an interaction with topoisomerase II. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Clinical use

As chemotherapy:  Actinomycin D, marketed under the trade name Dactinomycin, is one of the older chemotherapy drugs, and has been used in therapy for many years. It is a clear, yellow liquid administered intravenously and most commonly used in treatment of a variety of cancers including gestational trophoblastic neoplasia,  Wilms' tumor and rhabdomyosarcoma.

 As an antibiotic: It was the first antibiotic shown to have anti-cancer activity, but is not normally used as such, as it is highly toxic, causing damage to genetic material.

Research use: 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. From http://en.wikipedia.org/wiki/Dactinomycin.

DRUG DESCRIPTION

Dactinomycin is one of the actinomycins, a group of antibiotics produced by various species of Streptomyces. Dactinomycin is the principal component of the mixture of actinomycins produced by Streptomyces parvullus. Unlike other species of Streptomyces, this organism yields an essentially pure substance that contains only traces of similar compounds differing in the amino acid content of the peptide side chains. The empirical formula is C62H86N12O16. COSMEGEN is a sterile, yellow to orange lyophilized powder for injection by the intravenous route or by regional perfusion after reconstitution. Each vial contains 0.5 mg (500 mcg) of dactinomycin and 20.0 mg of mannitol.

Mechanism of Action

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 implants. 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.

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