Tellurite-induced oxidative stress leads to cell death of murine hepatocarcinoma cells.

Abstract

Data regarding tellurium (Te) toxicity are scarce. Studies on its metabolism, performed mainly in bacteria, underline a major role of reactive oxygen species (ROS). We investigated whether tellurite undergoes redox cycling leading to ROS formation and cancer cell death. The murine hepatocarcinoma Transplantable Liver Tumor (TLT) cells were challenged with tellurite either in the presence or in the absence of different compounds as N-acetylcysteine (NAC), 3-methyladenine, BAPTA-AM, and catalase. NAC inhibition of tellurite-mediated toxicity suggested a major role of oxidative stress. Tellurite also decreased both glutathione (GSH) and ATP content by 57 and 80%, respectively. In the presence of NAC however, the levels of such markers were almost fully restored. Tellurite-mediated ROS generation was assessed both by using the fluorescent, oxidation-sensitive probe dichlorodihydrofluorescein diacetate (DCHF-DA) and electron spin resonance (ESR) spectroscopy to detect hydroxyl radical formation. Cell death occurs by a caspase-independent mechanism, as shown by the lack of caspase-3 activity and no cleavage of poly(ADP-ribose)polymerase (PARP). The presence of gamma-H2AX suggests tellurite-induced DNA strand breaking, NAC being unable to counteract it. Although the calcium chelator BAPTA-AM did show no effect, the rapid phosphorylation of eIF2alpha suggests that, in addition to oxidative stress, an endoplasmic reticulum (ER) stress may be involved in the mechanisms leading to cell death by tellurite.

• Authors: Juan M Sandoval, Philippe Levêque, Bernard Gallez, Claudio C Vásquez, Pedro Buc Calderon
• Journal: Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine (Biometals) Vol. 23 Issue 4 Pg. 623-32 (Aug 2010) ISSN: 1572-8773 [Electronic] Netherlands
• PMID: 20213267 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Reactive Oxygen Species
• Adenosine Triphosphate
• Caspase 3
• Glutathione
• tellurous acid
• Tellurium

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Carcinoma, Hepatocellular (metabolism)
• Caspase 3 (metabolism)
• Cell Death (drug effects)
• Cell Line, Tumor
• Glutathione (metabolism)
• Humans
• Liver Neoplasms (metabolism)
• Mice
• Oxidative Stress (drug effects)
• Reactive Oxygen Species (metabolism)
• Tellurium (pharmacology)