title: The enhancement of propyl gallate-induced apoptosis in HeLa cells by a proteasome inhibitor MG132.
abstract: Propyl gallate (PG) used in processed food and medicinal preparations has been shown to induce cell death in normal and cancer cells. The inhibition of proteasome function has emerged as a useful strategy to maneuver apoptosis. Here, we investigated the combined effects of PG and MG132 (a proteasome inhibitor) on HeLa cells in relation to cell growth, cell death, reactive oxygen species (ROS) and glutathione (GSH). PG induced growth inhibition and apoptosis in HeLa cells, accompanied by the loss of mitochondrial membrane potential (MMP; ΔΨm), activation of caspase 3 and PARP cleavage. The levels of ROS and GSH depletion were increased in PG-treated HeLa cells. MG132 intensified apoptosis and PARP cleavage in PG-treated HeLa cells. MG132 also increased ROS levels including mitochondrial O2•-, MMP (ΔΨm) loss and GSH depletion in PG-treated HeLa cells. PG induced a G1 phase arrest of the cell cycle in HeLa cells, which was significantly prevented by MG132. MG132 alone inhibited HeLa cell growth via inducing the cell cycle arrests and triggering apoptosis. Conclusively, the inhibition of proteasome by MG132 plays a role as an enhancement factor in PG-induced apoptosis of HeLa cells via increasing ROS levels and GSH depletion.
authors.affiliation: Department of Physiology, Medical School, Institute for Medical Sciences, Chonbuk National University, JeonJu 561-180, Republic of Korea.
authors.forename: Bo Ra
authors.initials: BR
authors.lastname: You
authors.forename: Woo Hyun
authors.initials: WH
authors.lastname: Park
mesh_terms: D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D005978:Glutathione / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D011435:Propyl Gallate / Q000494:pharmacology* / Q000627:therapeutic use; D061988:Proteasome Inhibitors; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D061988:Proteasome Inhibitors; D017382:Reactive Oxygen Species; D011435:Propyl Gallate; D005978:Glutathione; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde