Protective mechanisms against the antitumor agent bleomycin: lessons from Saccharomyces cerevisiae.
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.
Ramotar
Dindial
D
Maisonneuve-Rosemont Hospital, Guy-Bernier Research Center, 5415 Boulevard de l'Assomption, H1T 2M4, Montreal, Quebec, Canada. dramotar@hmr.qc.ca
Wang
Huijie
H
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004247:DNA / Q000737:chemistry; D004260:DNA Repair; D004351:Drug Resistance; D005609:Free Radicals; D008956:Models, Chemical; D009687:Nuclear Proteins / Q000737:chemistry; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry; D015534:Trans-Activators / Q000737:chemistry
D000970:Antineoplastic Agents; D005609:Free Radicals; C096739:IMP2 protein, S cerevisiae; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D001761:Bleomycin; D004247:DNA; D003546:Cysteine Endopeptidases; C031262:bleomycin hydrolase