Involvement of reactive oxygen species in the enhancement of membrane lipid peroxidation by sonodynamic therapy with functionalized fullerenes

Nagahiko Yumita, Yumiko Iwase, Takahiro Watanabe, Koji Nishi, Hiroyuki Kuwahara, Masato Shigeyama, Kiyomi Sadamoto, Toshihiko Ikeda, Shin Ichiro Umemura

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5 Citations (Scopus)

Abstract

Background/Aim: 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 sonodynamicallyinduced antitumor effect with functionalized fullerenes, such as polyhydroxy fullerene (PHF. Materials and 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)6481-6487
Number of pages7
JournalAnticancer research
Volume34
Issue number11
Publication statusPublished - 2014 Nov 1

Keywords

  • Fullerenes
  • Membrane lipid peroxidation
  • Nanomedicine
  • Reactive oxygen species
  • Sarcoma 180
  • Sonodynamic therapy
  • Ultrasound

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Yumita, N., Iwase, Y., Watanabe, T., Nishi, K., Kuwahara, H., Shigeyama, M., Sadamoto, K., Ikeda, T., & Umemura, S. I. (2014). Involvement of reactive oxygen species in the enhancement of membrane lipid peroxidation by sonodynamic therapy with functionalized fullerenes. Anticancer research, 34(11), 6481-6487.