Cytotoxic effects of catechol to neuroblastoma N2a cells.

Abstract

The mechanisms of catechol-induced cytotoxicity were studied in cultures of neuroblastoma N2a cells. The minimal cytotoxic concentration after 72 h was 20 micromol x l(-1). The EC50 after 72 h was 38 micromol x l(-1). There was not a correlation between the cytotoxicity and the formation of quinones in the medium. Catechol-induced cytotoxicity was increased significantly when superoxide dismutase (SOD) was added. The addition of catalase did not protect cells, but this enzyme reverted the deleterious effect of SOD. The experimental studies showed a detrimental effect of deferoxamine on catechol-induced cytotoxicity suggesting that cells need iron to maintain its metabolism. NF-kappaB inhibitors increased the cytotoxicity, suggesting that this factor is also important for cell viability. L-cysteine and N-acetyl-L-cysteine protected cells significantly in a dose-dependent manner. The use of monochlorobimane showed that catechol induced reduced glutathione (GSH) depletion after 24 h, prior to cell death. The mode of cell death was studied by flow cytometry after double staining with annexin V and propidium iodide. Catechol induced apoptosis after 72 h. Furthermore, catechol also induced nuclear fragmentation. These data showed that catechol-induced cytotoxicity to N2a cell was not directly a consequence of reactive oxygen species production. Rather, it was due to GSH depletion followed by the induction of apoptosis.

• Authors: Rute M F Lima, Lisandro D G Alvarez, Maria F D Costa, Silvia L Costa, Jorge Clarêncio, Ramon S El-Bachá
• Journal: General physiology and biophysics (Gen Physiol Biophys) Vol. 27 Issue 4 Pg. 306-14 (Dec 2008) ISSN: 0231-5882 [Print] Slovakia
• PMID: 19202205 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Catechols
• Cytotoxins
• NF-kappa B
• Reactive Oxygen Species
• Sesquiterpenes
• parthenolide
• Superoxide Dismutase
• Glutathione
• Curcumin
• Deferoxamine
• Cysteine
• catechol
• Ascorbic Acid

Topics

• Animals
• Antioxidants (physiology)
• Apoptosis (drug effects, physiology)
• Ascorbic Acid (pharmacology)
• Catechols (pharmacology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Curcumin (pharmacology)
• Cysteine (pharmacology)
• Cytotoxins (pharmacology)
• Deferoxamine (pharmacology)
• Glutathione (metabolism)
• Mice
• NF-kappa B (metabolism)
• Neuroblastoma
• Reactive Oxygen Species (metabolism)
• Sesquiterpenes (pharmacology)
• Superoxide Dismutase (metabolism)