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Pharmaceuticals

Removing Sugar From Cancer Drug Eliminates Side Effect

Oncology: Deglycosylated bleomycin kills cancer in mice without causing lung damage

by Celia Henry Arnaud
February 26, 2016 | APPEARED IN VOLUME 94, ISSUE 8

Removing the disaccharide (red) from bleomycin eliminates the compound’s lung toxicity without altering its antitumor activity.

Bleomycin is used as a chemotherapeutic agent for multiple types of cancer, including Hodgkin’s lymphoma and melanoma. It causes severe lung damage in about 20% of patients who receive it, however, which limits its use. A team led by Philippe Bonniaud of Dijon University Hospital finds that snipping a disaccharide moiety off bleomycin reduces the lung toxicity in mice without reducing the anticancer activity (Sci. Transl. Med. 2016, DOI: 10.1126/scitranslmed.aad7785). The team studied the effects of bleomycin and deglycosylated bleomycin in mouse models of Hodgkin’s lymphoma and melanoma. After injecting the drugs into mice with human versions of the cancers, the researchers found that the deglycosylated bleomycin induced caspase-3-dependent apoptosis, which kills the cancer cells, but it did not activate caspase-1, which seems responsible for bleomycin’s lung toxicity. In addition, bleomycin, but not deglycosylated bleomycin, induced formation of inflammation-related molecules, including cytokines and reactive oxygen species, which are also associated with lung damage. However, the mechanism by which bleomycin damages lung tissue is still not fully understood, although caspase-1 seems to play a major role. More tests are needed to determine whether deglycosylated bleomycin can be substituted for bleomycin in patients.

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