Protection against arsenic trioxide-induced autophagic cell death in U118 human glioma cells by use of lipoic acid.
Arsenic is an environmental toxicant found naturally in ground water. Epidemiological studies have suggested a correlation between chronic arsenic exposure and potential brain tissue damage in clinical case and animal experiments. Lipoic acid (LA) is a thiol-compound naturally occurring in plants and animals, which is thought to be a strong antioxidant and possess neuroprotective effects. The objective of this study was to determine if the AS(2)O(3)-induced glial cell toxicity could be prevented by LA. The human malignant glioma cell (U118) was selected as a research model. By using acridine orange staining and flow cytometry analysis, we found that autophagic, but not apoptotic, cell death was significantly induced by AS(2)O(3) in U118 cells, and that AS(2)O(3)-mediated autophagic cell death was nearly completely attenuated by LA. Down-regulation of p53 and Bax proteins and the up-regulation of Bcl-2 and HSP-70 proteins were observed by western blot in AS(2)O(3)-mediated autophagic cell death. Our results implied that LA completely inhibited U118 cells autophagic cell death induced by AS(2)O(3). We suggested that LA may emerge as a useful protective agent against arsenic-induced glial cell toxicity and reversing arsenic-induced damage in human brain.
Cheng
Tain-Junn
TJ
Chimei Medical Center Tainan, Taiwan.
Wang
Ying-Jan
YJ
Kao
Wei-Wan
WW
Chen
Rong-Jane
RJ
Ho
Yuan-Soon
YS
D000165:Acridine Orange / Q000737:chemistry; D000975:Antioxidants / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D020261:Arsenic Poisoning / Q000517:prevention & control*; D000077237:Arsenic Trioxide; D001152:Arsenicals; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004347:Drug Interactions; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000737:chemistry; D005910:Glioma; D006801:Humans; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects*; D010087:Oxides / Q000633:toxicity*; D008063:Thioctic Acid / Q000494:pharmacology*
D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D001152:Arsenicals; D005456:Fluorescent Dyes; D010087:Oxides; D008063:Thioctic Acid; D000165:Acridine Orange; D000077237:Arsenic Trioxide