The effect of MG132, a proteasome inhibitor on HeLa cells in relation to cell growth, reactive oxygen species and GSH.

Abstract

MG132 (carbobenzoxy-Leu-Leu-leucinal) is a peptide aldehyde, which effectively blocks the proteolytic activity of the 26S proteasome complex. We evaluated the effects of MG132 on the growth of human cervix cancer HeLa cells in relation to the cell growth, reactive oxygen species (ROS) and glutathione (GSH) levels. Dose-dependent inhibition of cell growth was observed in HeLa cells with an IC50 of approximately 5 microM MG132 for 24 h. DNA flow cytometric analysis indicated that treatment with MG132 induced S, G2-M or non-specific phase arrests of the cell cycle dose-dependently. Treatment with MG132 induced apoptosis in a dose-dependent manner, as evidenced by sub-G1 cells and annexin V staining cells. Treatment with MG132 also induced the loss of mitochondrial membrane potential in HeLa cells. The intracellular ROS levels including O2*- were significantly increased in MG132-treated cells. Furthermore, the depletion of intracellular GSH content was observed in cells treated with MG132. In conclusion, MG132 inhibited the growth of HeLa cells via inducing the cell cycle arrest as well as triggering apoptosis. The changes of ROS and GSH by MG132 were closely related to apoptosis in HeLa cells.

• Authors: Yong Hwan Han, Hwa Jin Moon, Bo Ra You, Woo Hyun Park
• Journal: Oncology reports (Oncol Rep) Vol. 22 Issue 1 Pg. 215-21 (Jul 2009) ISSN: 1021-335X [Print] Greece
• PMID: 19513526 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Cysteine Proteinase Inhibitors
• Leupeptins
• Proteasome Inhibitors
• Reactive Oxygen Species
• Proteasome Endopeptidase Complex
• Glutathione
• benzyloxycarbonylleucyl-leucyl-leucine aldehyde

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Proliferation (drug effects)
• Cysteine Proteinase Inhibitors (pharmacology)
• Dose-Response Relationship, Drug
• Female
• Glutathione (metabolism)
• HeLa Cells
• Humans
• Inhibitory Concentration 50
• Leupeptins (pharmacology)
• Membrane Potential, Mitochondrial (drug effects)
• Proteasome Endopeptidase Complex (metabolism)
• Proteasome Inhibitors
• Reactive Oxygen Species (metabolism)
• Uterine Cervical Neoplasms (enzymology, pathology)