title: Human GM3 Synthase Attenuates Taxol-Triggered Apoptosis Associated with Downregulation of Caspase-3 in Ovarian Cancer Cells.
abstract: BACKGROUND
  Taxol (paclitaxel) inhibits proliferation and induces apoptosis in a variety of cancer cells, but it also upregulates cytoprotective proteins and/or pathways that compromise its therapeutic efficacy.
  
  
  METHODS
  The roles of GM3 synthase (α2,3-sialyltransferase, ST3Gal V) in attenuating Taxol-induced apoptosis and triggering drug resistance were determined by cloning and overexpressing this enzyme in the SKOV3 human ovarian cancer cell line, treating SKOV3 and the transfectants (SKOV3/GS) with Taxol and determining apoptosis, cell survival, clonogenic ability, and caspase-3 activation.
  
  
  RESULTS
  In this report, we demonstrated that Taxol treatment resulted in apoptosis which was associated with caspase-3 activation. Taxol treatment upregulated the expression of human GM3 synthase, an enzyme that transfers a sialic acid to lactosylceramide. Moreover, we cloned the full-length GM3 synthase gene and showed for the first time that forced expression of GM3 synthase attenuated Taxol-induced apoptosis and increased resistance to Taxol in SKOV3 cells.
  
  
  CONCLUSIONS
  GM3 synthase overexpression inhibited Taxol-triggered caspase-3 activation, revealing that upregulation of GM3 synthase prevents apoptosis and hence reduces the efficacy of Taxol therapy.
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University Simon Cancer Center, Indianapolis, USA.
authors.forename: Su
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University Simon Cancer Center, Indianapolis, USA.
authors.forename: Khadijeh
authors.initials: K
authors.lastname: Bijangi-Vishehsaraei
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Indiana University School of Medicine, Indianapolis, USA.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Saadatzadeh
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University Simon Cancer Center, Indianapolis, USA.
authors.forename: Ahmad R
authors.initials: AR
authors.lastname: Safa
keywords: Apoptosis; Caspase-8; Drug Resistance; GM3 Synthase; Ovarian Cancer; Taxol