title: Bevacizumab is superior to Temozolomide in causing mitochondrial dysfunction in human brain tumors.
abstract: OBJECTIVE
  Current chemotherapy treatments available for treating high-grade brain tumors, Temozolomide (TMZ) or Bevacizumab (BEV), not only have specific anti-tumor mechanisms, but also have an effect on mitochondria. However, effects of both drugs on mitochondria isolated from human brain tumors have not been thoroughly investigated. This study determined the direct effects of TMZ and BEV as well as the neurotoxic condition (calcium overload), on the function of mitochondria and compared these effects on mitochondria isolated from low- and high-grade human brain tumors.
  
  
  METHODS
  Mitochondria were isolated from either low- or high-grade human primary brain tumors. Calcium overload conditions (100 or 200 μM), TMZ (300 μM), and BEV (2 mg/mL) were applied to isolated mitochondria from low- and high-grade brain tumors. Following the treatment, mitochondrial function, including reactive oxygen species production, membrane potential changes, and swelling, were determined. The mitochondrial morphology was also examined.
  
  
  RESULTS
  In calcium overload conditions, mitochondrial dysfunction was only found to have occurred in low-grade tumors. In TMZ and BEV treatment, BEV, rather than TMZ, caused greater membrane depolarization and mitochondrial swelling in both grades of brain tumors.
  
  
  CONCLUSIONS
  TMZ and BEV can directly cause the dysfunction of mitochondria isolated from human brain tumors. However, BEV has a greater ability to disturb mitochondrial function in mitochondria isolated from human brain tumors than either TMZ or calcium overload conditions.
authors.affiliation: a Department of Anesthesiology, Faculty of Medicine , Chiang Mai University , Chiang Mai , Thailand.|b Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine , Chiang Mai University , Chiang Mai , Thailand.
authors.forename: Danop
authors.initials: D
authors.lastname: Nanegrungsunk
authors.affiliation: b Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine , Chiang Mai University , Chiang Mai , Thailand.
authors.forename: Nattayaporn
authors.initials: N
authors.lastname: Apaijai
authors.affiliation: b Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine , Chiang Mai University , Chiang Mai , Thailand.
authors.forename: Chontida
authors.initials: C
authors.lastname: Yarana
authors.affiliation: b Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine , Chiang Mai University , Chiang Mai , Thailand.
authors.forename: Jirapas
authors.initials: J
authors.lastname: Sripetchwandee
authors.affiliation: c Neurosurgery Division, Department of Surgery, Faculty of Medicine , Chiang Mai University , Chiang Mai , Thailand.
authors.forename: Kriengsak
authors.initials: K
authors.lastname: Limpastan
authors.affiliation: c Neurosurgery Division, Department of Surgery, Faculty of Medicine , Chiang Mai University , Chiang Mai , Thailand.
authors.forename: Wanarak
authors.initials: W
authors.lastname: Watcharasaksilp
authors.affiliation: c Neurosurgery Division, Department of Surgery, Faculty of Medicine , Chiang Mai University , Chiang Mai , Thailand.
authors.forename: Tanat
authors.initials: T
authors.lastname: Vaniyapong
authors.affiliation: b Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine , Chiang Mai University , Chiang Mai , Thailand.
authors.forename: Nipon
authors.initials: N
authors.lastname: Chattipakorn
authors.affiliation: b Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine , Chiang Mai University , Chiang Mai , Thailand.|d Department of Oral Biology and Diagnostic Science, Faculty of Dentistry , Chiang Mai University , Chiang Mai , Thailand.
authors.forename: Siriporn C
authors.initials: SC
authors.lastname: Chattipakorn
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D000068258:Bevacizumab / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000473:pathology*; D002122:Calcium Chloride / Q000494:pharmacology; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced; D005260:Female; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D017382:Reactive Oxygen Species / Q000378:metabolism; D012189:Retrospective Studies; D000077204:Temozolomide; D014407:Tumor Cells, Cultured
chemical_list: D020533:Angiogenesis Inhibitors; D018906:Antineoplastic Agents, Alkylating; D017382:Reactive Oxygen Species; D000068258:Bevacizumab; D003606:Dacarbazine; D002122:Calcium Chloride; D000077204:Temozolomide
keywords: Calcium overload; Human brain tumor; Mitochondria; Temozolomide and bevacizumab