G2/M blockade by paclitaxel induces caveolin-1 expression in A549 lung cancer cells: caveolin-1 as a marker of cytotoxicity.
Caveolins are highly expressed in terminally differentiated cells, but this expression is down-regulated in various cancer cell lines. Exposure to low doses of paclitaxel (taxol) is sufficient to up-regulate caveolin-1, suggesting that a mild cytotoxic stress induces a response implying caveolin and caveolae. Here we show that this up-regulation is sustained even after the cessation of paclitaxel treatment. After exposure to a cytostatic dose of paclitaxel (50 nM), A549 lung cancer cells are blocked in the G2/M cell cycle phase. After removal of paclitaxel, cell death occurs, accompanied with an increase in caveolin expression, suggesting an effect of caveolin in this process. Three days post-paclitaxel treatment, surviving A549 cells were passaged and only a half of them adhered to the culture dish. Adhering cells (still mainly in the G2/M cell cycle phase) were still unable to grow and progressively entered in an apoptotic state. This study suggests that effects of a low dose of paclitaxel were still present even 1 week after drug removal and that caveolin-1 is a good marker of cytotoxicity.
Roussel
Elise
E
Unité de Recherche en Pneumologie, Institut Universitaire de Cardiologie et de Pneumologie de l'Université Laval, Centre de Recherche Hôpital Laval, Université Laval, Sainte-Foy (Québec), Canada.
Bélanger
Martin M
MM
Couet
Jacques
J
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D051242:Caveolin 1; D022461:Caveolins / Q000096:biosynthesis*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms; D017239:Paclitaxel / Q000494:pharmacology*; D015854:Up-Regulation
D000972:Antineoplastic Agents, Phytogenic; C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins; D017239:Paclitaxel