Bleomycin is a glycosylated linear nonribosomal peptide antibiotic produced by the bacterium Streptomyces verticillus. Bleomycin refers to a family of structurally related compounds. When used as an anti-cancer agent, the chemotherapeutical forms are primarily bleomycin A₂ and B₂. Bleomycin A₂ is shown in the image. The drug is used in the treatment of lymphomas (especially Hodgkin's disease), squamous cell carcinomas, and testicular cancer as well as pleurodesis.

History

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Bleomycin was first discovered in 1962 when the Japanese scientist Hamao Umezawa found anti-cancer activity while screening culture filtrates of S. verticullus. Umezawa published his discovery in 1966. The drug was launched in Japan by Nippon Kayaku in 1969. In the US bleomycin gained Food and Drug Administration (FDA) approval in July 1973. It was initially marketed in the US by the Bristol-Myers Squibb precursor Bristol Laboratories under the brand name Blenoxane.

Suppliers

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Bristol-Myers Squibb still supplies Blenoxane. There are also generic versions of bleomycin available from Bedford, Sicor and Mayne Pharma.

Mechanism of action

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Bleomycin acts by induction of DNA strand breaks. Some studies suggest that bleomycin also inhibits incorporation of thymidine into DNA strands. DNA cleavage by bleomycin depends on oxygen and metal ions, at least in vitro. It is believed that bleomycin chelates metal ions (primarily iron) producing a pseudoenzyme that reacts with oxygen to produce superoxide and hydroxide free radicals that cleave DNA. In addition, these complexes also mediate lipid peroxidation and oxidation of other cellular molecules.

Side effects

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The most serious complication of bleomycin is pulmonary fibrosis and impaired lung function. Other side effects include fever, rash, hyperpigmentation, alopecia, and Raynaud's phenomenon.

References

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Chemotherapeutic agents | Metalloproteins

Bleomycin | Bléomycine | Bleomisin