title: Involvement of reactive oxygen species in the enhancement of membrane lipid peroxidation by sonodynamic therapy with functionalized fullerenes.
abstract: OBJECTIVE
  Sonodynamic cancer therapy is based on the preferential uptake and/or retention of a sonosensitizing drug (sonosensitizer) in tumor tissues and subsequent activation of the drug by ultrasound irradiation. In the present study, we investigated the participation of lipid peroxidation in the mechanism of the sonodynamically-induced antitumor effect with functionalized fullerenes, such as polyhydroxy fullerene (PHF.
  
  
  METHODS
  Ultrasonically-induced cell damage and lipid peroxidation with PHF were compared in the same in vitro insonation setup. Sarcoma 180 cells suspended in PBS were exposed to 2 MHz ultrasound in the presence and absence of PHF. Cell viability was determined by the Trypan Blue exclusion test. Lipid peroxidation in cell membranes was estimated by measuring the amount of malondialdehyde as the thiobarbituric acid-reactive-substances.
  
  
  RESULTS
  Significant enhancement of the rates of both ultrasonically-induced cell damage and lipid peroxidation was observed in the presence of PHF, both of which were positively correlated with PHF. The enhancement of cell damage and lipid peroxidation with PHF was suppressed by reactive oxygen scavengers such as histidine and tryptophan.
  
  
  CONCLUSIONS
  The good correlation observed in the presence of PHF suggests that membrane lipid peroxidation is one of the important intermediary events in sonodynamically-induced cellular damage. The inhibitory effects of histidine and tryptophan also provide evidence that singlet oxygen plays an important role in PHF-mediated sonosensitization of membranes and that this moiety may be an important mediator of cell destruction in sonodynamic therapy associated with PHF and ultrasound.
authors.affiliation: Yokohama College of Pharmacy, Yokohama, Kanagawa, Japan n.yumita@hamayaku.ac.jp.
authors.forename: Nagahiko
authors.initials: N
authors.lastname: Yumita
authors.affiliation: Yokohama College of Pharmacy, Yokohama, Kanagawa, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Iwase
authors.affiliation: Yokohama College of Pharmacy, Yokohama, Kanagawa, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Yokohama College of Pharmacy, Yokohama, Kanagawa, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Nishi
authors.affiliation: Yokohama College of Pharmacy, Yokohama, Kanagawa, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuwahara
authors.affiliation: Yokohama College of Pharmacy, Yokohama, Kanagawa, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Shigeyama
authors.affiliation: Yokohama College of Pharmacy, Yokohama, Kanagawa, Japan.
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Sadamoto
authors.affiliation: Yokohama College of Pharmacy, Yokohama, Kanagawa, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ikeda
authors.affiliation: Department of Electrical and Communication Engineering, Tohoku University, Aoba-ku, Sendai, Japan.
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Umemura
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D003131:Combined Modality Therapy; D005260:Female; D037741:Fullerenes / Q000737:chemistry / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D051379:Mice; D008813:Mice, Inbred ICR; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012510:Sarcoma 180 / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D014407:Tumor Cells, Cultured; D014464:Ultrasonic Therapy
chemical_list: D037741:Fullerenes; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species
keywords: Ultrasound; fullerenes; membrane lipid peroxidation; nanomedicine; reactive oxygen species; sarcoma 180; sonodynamic therapy