Roles of glutathione

A decrease in the glutathione (GSH) level that increases the intracellular level of ROS predisposes cells to DNA damage. It has been reported that arsenic-induced apoptosis appeared to be associated with changes in GSH levels.49,51,55 GSH appears to be a key player in determining the consequences of arsenic exposure including whether apoptosis will take place. The sensitivity of various tumor cell lines to As2O3-induced growth inhibition and apoptosis has been shown to be inversely related to the intracellular GSH concentration.10 As arsenic binds to sulfhydryl group-containing GSH, in cells with a low GSH

content, the capacity to eliminate ROS will be decreased. This results in the increase in ROS level, which causes the activation of caspase-3.45,58 The antioxidant NAC, which increased the synthesis of GSH, completely suppressed As2O3-induced apoptosis.17 In contrast, buthionine sulfoximine (BSO), a depleter of cellular GSH, and ascorbic acid, which decreased the intracellular GSH content, substantially enhanced the effect of As2O3.10,46,49,51 In addition, the increased resistance to arsenic displayed by NB4/As cells may be related to a high intracellular GSH level because reduction of the GSH level by BSO completely restored the sensitivity of these cells to arsenic.55 Therefore, the intracellular GSH level could be a good indicator for the sensitivity of various cancer cells to arsenic.

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