Actinomycin
Encyclopedia
The actinomycins are a class of polypeptide antibiotics
Polypeptide antibiotics
Polypeptide antibiotics are diverse class of antibiotics used for eye, ear or bladder infections in addition to aminoglycosides. They are too toxic to be suitable for systemic administration, but can safely be administered topically on the skin...

 isolated from soil bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

 of the genus Streptomyces
Streptomyces
Streptomyces is the largest genus of Actinobacteria and the type genus of the family Streptomycetaceae. Over 500 species of Streptomyces bacteria have been described. As with the other Actinobacteria, streptomycetes are gram-positive, and have genomes with high guanine and cytosine content...

, of which the most significant is actinomycin D. It was the first antibiotic isolated by Selman Waksman
Selman Waksman
Selman Abraham Waksman was an American biochemist and microbiologist whose research into organic substances—largely into organisms that live in soil—and their decomposition promoted the discovery of Streptomycin, and several other antibiotics...

 and his co-worker H. B. Woodruff in 1940.



Mechanism

Actinomycin D is primarily used as an investigative tool in cell biology to inhibit transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...

. It does this by binding DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 at the transcription initiation complex and preventing elongation by RNA polymerase
RNA polymerase
RNA polymerase is an enzyme that produces RNA. In cells, RNAP is needed for constructing RNA chains from DNA genes as templates, a process called transcription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses...

. Because it can bind DNA duplexes, it can also interfere with DNA replication
DNA replication
DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...

, although other chemicals such as hydroxyurea
Hydroxyurea
Hydroxycarbamide or hydroxyurea is an antineoplastic drug, first synthesized in 1869, used in myeloproliferative disorders, specifically polycythemia vera and essential thrombocythemia...

 are better suited for use in the laboratory as inhibitors of DNA synthesis.

As chemotherapy

Actinomycin D, also known generically as dactinomycin, was approved by the US FDA on December 10, 1964 and launched by Merck, Sharpe and Dohme under the trade name Cosmegen. It 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
Wilms' tumor
Wilms' tumor or nephroblastoma is cancer of the kidneys that typically occurs in children, rarely in adults.Its common name is an eponym, referring to Dr. Max Wilms, the German surgeon who first described this kind of tumor....

 and rhabdomyosarcoma
Rhabdomyosarcoma
A rhabdomyosarcoma is a type of cancer, specifically a sarcoma , in which the cancer cells are thought to arise from skeletal muscle progenitors. It can also be found attached to muscle tissue, wrapped around intestines, or in any anatomic location...

.

As an antibiotic

It was the first antibiotic shown to have anti-cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

 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
Fluorescence
Fluorescence is the emission of light by a substance that has absorbed light or other electromagnetic radiation of a different wavelength. It is a form of luminescence. In most cases, emitted light has a longer wavelength, and therefore lower energy, than the absorbed radiation...

 derivative, 7-aminoactinomycin D (7-AAD), are used as stains in microscopy
Microscopy
Microscopy is the technical field of using microscopes to view samples and objects that cannot be seen with the unaided eye...

 and flow cytometry
Flow cytometry
Flow cytometry is a technique for counting and examining microscopic particles, such as cells and chromosomes, by suspending them in a stream of fluid and passing them by an electronic detection apparatus. It allows simultaneous multiparametric analysis of the physical and/or chemical...

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.
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