Bleomycin and its role in inducing apoptosis and senescence in lung cells - modulating effects of caveolin-1.
Bleomycin, a widely used anti-tumor agent, is well-known to cause single- and double-strand breaks in cellular DNA in vivo and in vitro leading finally to genomic instability of damaged cells. Bleomycin causes an increase of reactive oxygen species resulting in oxidative stress and pulmonary fibrosis. Further, bleomycin induces apoptosis and senescence in epithelial and non-epithelial cells of the lung. Caveolin-1 is a scaffold protein of caveolae, which are particularly abundant in alveolar epithelial type I cells, in endothelial and smooth muscle cells, and in fibroblasts of lung tissue. Caveolin-1 directly interacts with signaling molecules and effects diverse signaling pathways regulating cell proliferation, apoptosis, differentiation and growth. In this review we discuss aspects of bleomycin resistance. We summarize recent data about the effects of bleomycin in terms of lung cell biology and emphasize that bleomycin-induced injury of lung cells is accompanied by altered expression levels of caveolin-1. Caveolin-1 is involved in bleomycin-induced apoptosis and senescence of normal and lung cancer cells. Investigating the role of caveolin-1 may provide new tools for therapeutic interventions in lung disease and for the understanding of tumor biology.
Kasper
Michael
M
Institute of Anatomy, Medical Faculty Carl Gustav Carus, University of Technology Dresden, 01307 Dresden, Germany. michael.kasper@tu-dresden.de
Barth
Kathrin
K
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001761:Bleomycin / Q000494:pharmacology* / Q000627:therapeutic use; D051242:Caveolin 1 / Q000494:pharmacology*; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology*; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D008171:Lung Diseases / Q000503:physiopathology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D019098:Telomerase / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D051242:Caveolin 1; D001761:Bleomycin; D019098:Telomerase