• Saturday February 22,2020

Actinomycin D

Actinomycin D is a cytotoxic antibiotic also known as dactinomycin. As a cytostatic agent that inhibits cell growth and cell division, Actinomycin D is used to treat cancers. It is available under the trade names Lyovac-Cosmegen® and Cosmegen®.

What is actinomycin D?

Because actinomycin D inhibits cell growth and cell division as a cytostatic agent, actinomycin D is used to treat cancers.

The peptide antibiotic actinomycin D is obtained from the soil bacteria Streptomyces parvulus. The drug is composed of two cyclic peptides linked by a phenoxazine compound. The cytostatic drug was first described in 1949.

Initially, the scientists hoped to have found an antibiotic for treating bacterial diseases with actinomycin D. But it quickly became clear how toxic the drug is to human cells.

Therefore, doctors soon instead used it in the treatment of various tumors. The cytostatic drug is intended to prevent the rapid proliferation of cancer cells in both adults and children during chemotherapy.

Pharmacological action

Actinomycin D binds to the DNA (deoxyribonucleic acid) of the cells, which prevents the double helix from opening. Those skilled in the art refer to this process, in which an agent entraps molecules into the DNA and cross-links them, as an intercalation.

Actinomycin D binds mainly to the guanine residues of DNA. Actinomycin D initially inhibits RNA synthesis at low doses. As a result, the production of proteins in the cells is minimized. At higher doses, DNA replication is also affected. The genetic material is thus no longer reproduced, whereby the cell division is absent.

The tumor is thereby inhibited from growing. Because actinomycin D can not penetrate the blood-brain barrier in the human body, tumors in the brain and spinal cord can not be treated with the drug. All other cells of the body that contain DNA can be affected by the drug. Because actinomycin D does not have a specific effect on the tumor, but also on the healthy body cells.

Medical application & use

The active ingredient actinomycin D is used in various solid tumors. These include Ewing's sarcoma, a common bone cancer in both children and adults. But even in malignant tumors of the soft tissues (soft tissue sarcoma and rhabdomyosarcoma) doctors use the cytostatic properties of Actinomycin D.

Likewise, the drug is used in children and adolescents during the treatment of a malignant kidney tumor (nephroblastoma). Adults with testicular carcinoma, choriocarcinoma or Kaposi's sarcoma can also be treated with actinomycin D. Actinomycin D is combined with other cytostatic drugs in all of these chemotherapies.

It is also administered several times at precisely defined intervals over a longer period of time. Because after just one week, about 30 percent of the drug is excreted through the urine and the stool again. Because Actinomycin D is highly irritating, it is only given intravenously and can not be taken orally. Due to the severe tissue damage, the doctors carefully control the injection site during treatment.

Risks & Side Effects

Since actinomycin D inhibits the growth and division of human cells, it can lead to different side effects. Among other things, the drug disturbs the development of blood cells. This can lead to a temporary lack of platelets and white blood cells.

The latter in turn has the consequence that infections by bacteria, fungi and viruses frequently occur. Direct contact with the drug can severely damage and even kill both the skin and the eyes as well as the connective tissue. The injection must therefore be made only in the vein and not in the adjacent tissue. The damage can be particularly serious after a previous irradiation, which is why actinomycin D should never be used after radiotherapy.

Very often, nausea and vomiting occur just hours after the administration of actinomycin D. Also, painful mucosal damage (mucositis) in the mouth, esophagus and intestine may occur. Also, the agent can attack the liver. Because Actinomycin D is mutagenic and embryotoxic, it can cause lasting damage to the genome and must not be used during pregnancy.

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