Carbobenzoxy-
Leu-Leu-
leucinal (
MG132) as a
proteasome inhibitor has been shown to induce apoptotic cell death through formation of
reactive oxygen species (ROS). In the present study, we evaluated the effects of
MG132 on the growth of A549
lung cancer cells in relation to cell growth, ROS and
glutathione (GSH) levels. Treatment with
MG132 inhibited the growth of A549 cells with an IC(50) of approximately 20 microM at 24 hours.
DNA flow cytometric analysis indicated that 0.5 approximately 30 microM
MG132 induced a G1 phase arrest of the cell cycle in A549 cells. Treatment with 10 or 30 microM
MG132 also induced apoptosis, as evidenced by sub-G1 cells and
annexin V staining cells. This was accompanied by the loss of mitochondrial membrane potential (
MMP; Delta psi m). The intracellular ROS levels including O(2) (*-) were strongly increased in 10 or 30 microM MG132-treated A549 cells but were down-regulated in 0.1, 0.5 or 1 microM MG132-treated cells. Furthermore, 10 or 30 microM
MG132 increased mitochondrial O(2) (*- ) level but 0.1, 0.5 or 1 microM
MG132 decreased that. In addition, 10 or 30 microM
MG132 induced GSH depletion in A549 cells. In conclusion,
MG132 inhibited the growth of human A549 cells via inducing the cell cycle arrest as well as triggering apoptosis, which was in part correlated with the changes of ROS and GSH levels. Our present data provide important information on the anti-growth mechanisms of
MG132 in A549
lung cancer cells in relation to ROS and GSH.