title: Effects of quercetin nanoliposomes on C6 glioma cells through induction of type III programmed cell death.
abstract: BACKGROUND
  Quercetin has been shown to induce apoptosis in a number of cancer cell lines, but a quercetin-loaded nanoliposomal formulation with enhanced antitumor activity in C6 glioma cells and its effect on cancer cell death has not been well studied. The aim of this study was to examine if quercetin-loaded liposomes (QUE-NL) has enhanced cytotoxic effects and if such effects involve type III programmed cell death in C6 glioma cells.
  
  
  METHODS
  C6 glioma cells were treated with QUE-NL and assayed for cell survival, apoptosis, and necrosis. Levels of reactive oxygen species production and loss of mitochondrial membrane potential (ΔΨm) were also determined by flow cytometry assay to assess the effects of QUE-NL. ATP levels and lactate dehydrogenase activity were measured, and Western blotting was used to assay cytochrome C release and caspase expression.
  
  
  RESULTS
  QUE-NL induced type III (necrotic) programmed cell death in C6 glioma cells in a dose-dependent and time-dependent manner. High concentrations of QUE-NL induced cell necrosis, which is distinct from apoptosis and autophagy, whereas liposomes administered alone induced neither significant apoptosis nor necrosis in C6 glioma cells. QUE-NL-induced ΔΨm loss and cytochrome C release had no effect on caspase activation, but decreased ATP levels and increased lactate dehydrogenase activity indicated that QUE-NL stimulated necrotic cell death.
  
  
  CONCLUSIONS
  C6 glioma cells treated with QUE-NL showed a cellular pattern associated with necrosis without apoptosis and was independent of caspase activity. Nonapoptotic cell death induced by high concentrations of QUE-NL for controlling caspase-independent type III programmed cell death may provide the basis for novel therapeutic approaches to overcome avoidance of apoptosis by malignant cells.
authors.affiliation: Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan City, Hubei Province, People's Republic of China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Jun Jie
authors.initials: JJ
authors.lastname: Wang
authors.forename: Guang Yi
authors.initials: GY
authors.lastname: Yang
authors.forename: Shi Ming
authors.initials: SM
authors.lastname: Du
authors.forename: Nan
authors.initials: N
authors.lastname: Zeng
authors.forename: Dong Sheng
authors.initials: DS
authors.lastname: Li
authors.forename: Rui Ming
authors.initials: RM
authors.lastname: Li
authors.forename: Ji Yan
authors.initials: JY
authors.lastname: Chen
authors.forename: Jin Bo
authors.initials: JB
authors.lastname: Feng
authors.forename: Shen Hao
authors.initials: SH
authors.lastname: Yuan
authors.forename: Fang
authors.initials: F
authors.lastname: Ye
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry*; D009336:Necrosis; D011794:Quercetin / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D008081:Liposomes; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D011794:Quercetin; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3; D053453:Caspase 9