Downregulation of caveolin-1 affects bleomycin-induced growth arrest and cellular senescence in A549 cells

Bleomycin is an anti-cancer drug that induces both apoptosis and senescence, two processes thought to involve caveolin-1. Here we investigate the role of caveolin-1 in bleomycin-induced senescence. We show that bleomycin-treated A549 cells exhibit: senescence-like cell morphology; a senescence-associated increase in SA-beta-galactosidase activity; cell cycle arrest; and upregulation of p53 and p21. As predicted, we find that caveolin-1 amount increases in response to bleomycin-treatment and that modulation of caveolin-1 affects p21 and p53 levels, cell cycling, and senescence (SA-beta-galactosidase activity). Interestingly, senescence-associated cell cycle arrest via p53 and p21 and SA-beta-galactosidase activity is reduced in young A549 cells when short hairpin RNA specific for caveolin-I was applied before bleomycin-treatment. Our results support the hypothesis that down regulation of caveolin-I expression affects bleomycin-induced cell cycle arrest and subsequent cellular senescence that is driven by p53 and p21. 16k, (c) 2007 Published by Elsevier Ltd.