Protection against arsenic trioxide-induced autophagic cell death in U118 human glioma cells by use of lipoic acid

Tain Junn Cheng, Ying-Jan Wang, Wei Wan Kao, Rong-Jane Chen, Yuan Soon Ho

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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 AS2O3-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 AS2O3 in U118 cells, and that AS2O3-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 AS2O3-mediated autophagic cell death. Our results implied that LA completely inhibited U118 cells autophagic cell death induced by AS2O3. 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.

Original languageEnglish
Pages (from-to)1027-1038
Number of pages12
JournalFood and Chemical Toxicology
Volume45
Issue number6
DOIs
Publication statusPublished - 2007 Jun 1

Fingerprint

lipoic acid
Thioctic Acid
autophagy
Autophagy
Cell death
arsenic
Glioma
Arsenic
neuroglia
Neuroglia
cells
Toxicity
cytotoxicity
Brain
Animals
brain
Protective Agents
bcl-2-Associated X Protein
neuroprotective effect
acridine orange

All Science Journal Classification (ASJC) codes

  • Food Science
  • Toxicology

Cite this

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abstract = "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 AS2O3-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 AS2O3 in U118 cells, and that AS2O3-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 AS2O3-mediated autophagic cell death. Our results implied that LA completely inhibited U118 cells autophagic cell death induced by AS2O3. 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.",
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Protection against arsenic trioxide-induced autophagic cell death in U118 human glioma cells by use of lipoic acid. / Cheng, Tain Junn; Wang, Ying-Jan; Kao, Wei Wan; Chen, Rong-Jane; Ho, Yuan Soon.

In: Food and Chemical Toxicology, Vol. 45, No. 6, 01.06.2007, p. 1027-1038.

Research output: Contribution to journalArticle

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