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Dactinomycin, also known as actinomycin D, is a chemotherapy medication used to treat a number of types of
cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Poss ...
. This includes Wilms tumor,
rhabdomyosarcoma Rhabdomyosarcoma (RMS) is a highly aggressive form of cancer that develops from mesenchymal cells that have failed to fully differentiate into myocytes of skeletal muscle. Cells of the neoplasm, tumor are identified as rhabdomyoblasts. There are ...
, Ewing's sarcoma, trophoblastic neoplasm,
testicular cancer Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system. Symptoms may include a lump in the testicle, or swelling or pain in the scrotum. Treatment may result in infertility. Risk factors include ...
, and certain types of
ovarian cancer Ovarian cancer is a cancerous ovarian tumor, tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the peritoneum, inner lining of the abdomen. The ovary is made ...
. It is given by injection into a vein. Most people develop side effects. Common side effects include bone marrow suppression, vomiting, mouth ulcers, hair loss, liver problems, infections, and muscle pains. Other serious side effects include future cancers, allergic reactions, and
tissue death Necrosis () is a form of cell injury Cell damage (also known as cell injury) is a variety of changes of stress that a Cell (biology), cell suffers due to external as well as internal environmental changes. Amongst other causes, this can be due ...
at the site of injection. Use in
pregnancy Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occur ...
may harm the baby. Dactinomycin is in the cytotoxic antibiotic family of medications. It is believed to work by blocking the creation of RNA. Dactinomycin was approved for medical use in the United States in 1964. It is on the
World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...
.


Medical use

Actinomycin is a clear, yellowish liquid administered intravenously and most commonly used in treatment of a variety of cancers, including: * Gestational trophoblastic neoplasia * Wilms' tumor *
Rhabdomyosarcoma Rhabdomyosarcoma (RMS) is a highly aggressive form of cancer that develops from mesenchymal cells that have failed to fully differentiate into myocytes of skeletal muscle. Cells of the neoplasm, tumor are identified as rhabdomyoblasts. There are ...
* Ewing's sarcoma *Malignant hydatidiform mole Sometimes it will be combined with other drugs in chemotherapy regimens, like the VAC regimen (with vincristine and
cyclophosphamide Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to immunosuppressant, suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian can ...
) for treating rhabdomyosarcoma and Ewing's sarcoma. It is also used as a radiosensitizer in adjunct to radiotherapies, since it can increase the radiosensitivity of tumor cells by inhibiting repair of sublethal radiation damage and delay the onset of the compensatory hyperplasia that occurs following irradiation.


Side effects

Common
adverse drug reaction An adverse drug reaction (ADR) is a harmful, unintended result caused by taking medication. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs. The meaning of this term ...
includes bone marrow suppression,
fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...
,
hair loss Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body. Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scarrin ...
, mouth ulcer,
loss of appetite Anorexia is a medical term for a loss of appetite Appetite is the desire to eat food items, usually due to Hunger (physiology), hunger. Appealing foods can stimulate appetite even when hunger is absent, although appetite can be greatly reduced ...
and
diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin ...
. Actinomycin is a vesicant, if extravasation occurs.


Mechanism

In
cell biology Cell biology (also cellular biology or cytology) is a branch of biology that studies the Anatomy, structure, Physiology, function, and behavior of cell (biology), cells. All living organisms are made of cells. A cell is the basic unit of life th ...
, actinomycin D is shown to have the ability to inhibit
transcription Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...
. Actinomycin D does this by binding DNA at the transcription initiation complex and preventing elongation of RNA chain by
RNA polymerase In molecular biology, RNA polymerase (abbreviated RNAP or RNApol), or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that synthesizes RNA from a DNA template. Using the enzyme helicase, RNAP locally opens the d ...
.


History

Actinomycin D was the first
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy, ...
shown to have anti-
cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Poss ...
activity. It was first isolated by
Selman Waksman Selman Abraham Waksman (July 22, 1888 – August 16, 1973) was a Jewish Russian-born American inventor, Nobel Prize laureate, biochemist and microbiologist whose research into the decomposition of organisms that live in soil enabled the discover ...
and his co-worker H. Boyd Woodruff in 1940. It was approved by the U.S.
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) on December 10, 1964, and launched by Merck Sharp and Dohme under the trade name Cosmegen.


Research use

Because actinomycin can bind DNA duplexes, it can also interfere with
DNA replication In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all life, living organisms acting as the most essential part for heredity, biologi ...
, although other chemicals such as
hydroxyurea Hydroxycarbamide, also known as hydroxyurea, is a medication used in sickle-cell disease, essential thrombocythemia, chronic myelogenous leukemia, polycythemia vera, and cervical cancer. In sickle-cell disease it increases fetal hemoglobin and d ...
are better suited for use in the laboratory as inhibitors of DNA synthesis. Actinomycin D and its
fluorescent Fluorescence is the emission of light by a substance that has absorbed light or other electromagnetic radiation. It is a form of luminescence. In most cases, the emitted light has a longer wavelength, and therefore a lower photon energy, tha ...
derivative, 7-aminoactinomycin D (7-AAD), are used as stains in
microscopy Microscopy is the technical field of using microscopes to view objects and areas of objects that cannot be seen with the naked eye (objects that are not within the resolution range of the normal eye). There are three well-known branches of micr ...
and
flow cytometry Flow cytometry (FC) is a technique used to detect and measure physical and chemical characteristics of a population of cells or particles. In this process, a sample containing cells or particles is suspended in a fluid and injected into the fl ...
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.


References


External links

* {{portal bar, Medicine Polypeptide antibiotics DNA replication inhibitors Depsipeptides Cyclic peptides IARC Group 3 carcinogens World Health Organization essential medicines Wikipedia medicine articles ready to translate DNA intercalaters