G2/M blockade by paclitaxel induces caveolin-1 expression in A549 lung cancer cells: caveolin-1 as a marker of cytotoxicity

Anticancer Drugs. 2004 Nov;15(10):961-7. doi: 10.1097/00001813-200411000-00005.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis
  • Caveolin 1
  • Caveolins / biosynthesis*
  • Cell Division / drug effects*
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • G2 Phase / drug effects*
  • Humans
  • Lung Neoplasms
  • Paclitaxel / pharmacology*
  • Up-Regulation

Substances

  • Antineoplastic Agents, Phytogenic
  • CAV1 protein, human
  • Caveolin 1
  • Caveolins
  • Paclitaxel