Suppression of staurosporine-mediated apoptosis in Hs578T breast cells through inhibition of neutral-sphingomyelinase by caveolin-1

Cancer Lett. 2007 Oct 18;256(1):64-72. doi: 10.1016/j.canlet.2007.05.007. Epub 2007 Jul 5.

Abstract

Caveolin-1, a 21-24kDa integral membrane protein, is a principal structural component of caveolae in vivo. To investigate the roles of caveolin-1, we established stable transfectants in Hs578T breast adenocarcinoma cells that had up- and down-regulated caveolin-1 expression. In the paper, we demonstrated that caveolin-1 overexpression in Hs578T cells significantly reduced staurosporine-induced apoptosis and the levels of caveolin-1 expression positively correlated with the number of colonies and colony size in soft agar. Our findings indicate for the first time in Hs578T cells that caveolin-1 might play a pivotal role in regulating apoptosis as a suppressor rather than a facilitator through inhibition of neutral-sphingomyelinase, decrease of ceramide, furthermore, activation of Akt signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Blotting, Western
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Caveolin 1 / pharmacology*
  • Ceramides / metabolism
  • Humans
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Sphingomyelin Phosphodiesterase / antagonists & inhibitors*
  • Staurosporine / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Caveolin 1
  • Ceramides
  • Proto-Oncogene Proteins c-akt
  • SMPD3 protein, human
  • Sphingomyelin Phosphodiesterase
  • Staurosporine