Alpha-class
glutathione transferases (α-
GSTs) have been shown to protect cells from the harmful effects of
reactive oxygen species (ROS) induced lipid peroxidation (LPO) during oxidative stress caused by various physico-chemical agents. While GSTA1-1/A2-2
isozymes exhibit high activity towards
lipid and
fatty acid hydroperoxides through their
selenium independent glutathione peroxidase (GPx) activity, the GSTA4-4
isozyme efficiently metabolizes the LPO product
4-hydroxynonenal (4-HNE) by conjugating it with
glutathione (GSH). Because of the fact that ROS generated by the chemopreventive agents,
sulforaphane (SFN) and
curcumin (Cur), are implicated in the mechanisms of
cancer cell killing, the present studies were designed to investigate the contribution of ROS induced LPO in the cytotoxic effects of these agents and the role of α-class
GSTs in modulating their toxicity. Human erythroleukemic (HL60) cells were stably transfected with the
cDNA encoding the hGSTA1-1 and
mGsta4-4 isozymes. After analysing the expression and activities of the respective GST
isozymes, the effects of SFN and Cur on the extent of LPO, cytotoxicity and apoptosis were compared in empty vector (VT), hGSTA1-1 and
mGsta4-4 expressing HL60 cells. These studies demonstrate that when compared with SFN, Cur was relatively more cytotoxic to HL60 cells. The ectopic expression of hGSTA1-1 and
mGsta4-4 isozymes provided resistance to SFN and Cur induced cytotoxicity and apoptosis through a significant suppression of LPO in these cells. Overall, the results suggest that the expression of α-class
GSTs in
cancer cells can modulate the therapeutic efficacy of chemopreventive agents.