Protective mechanisms against the antitumor agent bleomycin: lessons from Saccharomyces cerevisiae

Abstract

Bleomycin is a small glycopeptide antibiotic used in combination therapy for the treatment of a few types of human cancer. The antitumor effect of bleomycin is most likely caused by its ability to bind to DNA and induce the formation of toxic DNA lesions via a free radical reactive (Fe.bleomycin) complex. However, the chemotherapeutic potential of bleomycin is limited, as it causes pulmonary fibrosis and tumor resistance at high doses. The chemical structure and modes of action of bleomycin have been extensively studied and these provide a foundation towards improving the therapeutic value of the drug. This review provides a first account of the current state of knowledge of the cellular processes that can allow the yeast Saccharomyces cerevisiae to evade the lethal effects of bleomycin. This model organism is likely to provide rapid clues in our understanding of bleomycin resistance in tumor cells.